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1.
Differentiation ; 63(5): 253-62, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9810704

RESUMEN

Cell lines were established by a two-step method from osteomas which had been induced by infection of mice with RFB MuLV, a bone-pathogenic, replication-competent murine retrovirus. The benign tumors, consisting of mature lamellar bone and surrounded by a thin periosteum, were cultured on sponges of denatured collagen type I fibres for up to 4 weeks. At this time osteoma cells had grown into the collagenous matrix. After release and further cultivation in monolayers, the cell lines established from these cultures varied in morphology; they expressed T1, collagen type I and type III, alkaline phosphatase, osteonectin and osteopontin mRNAs at variable levels, but not osteocalcin/BGP. They also showed alkaline phosphatase activity, but lacked responsiveness to parathyroid hormone. All cell lines established from infected mice expressed retroviral and c-myc mRNA and viral protein. In contrast to cells from control mice they showed an extended life span in culture. After growth in a three-dimensional (3-D) collagen sponge culture the cells formed an extracellular matrix containing collagen type I, alkaline phosphatase and osteocalcin/BGP. These data indicate that the two-step method facilitates the establishment of osteoblast-like cell lines from osteomas and calvaria of old mice, and provides means for further analyses of retrovirus-induced skeletal pathogenesis and bone induction.


Asunto(s)
Neoplasias Óseas/virología , Virus de la Leucemia Murina/fisiología , Osteoblastos/citología , Osteoma/virología , Infecciones por Retroviridae/virología , Fosfatasa Alcalina/metabolismo , Animales , Neoplasias Óseas/patología , Diferenciación Celular/fisiología , División Celular/fisiología , Ratones , Ratones Endogámicos CBA , Ratones Endogámicos , Osteoma/patología , Hormona Paratiroidea/metabolismo , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Células Tumorales Cultivadas , Replicación Viral
2.
Bioelectromagnetics ; 19(4): 222-31, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9581965

RESUMEN

Human osteoblastic cells were grown in a three-dimensional (3-D) cell culture model and used to test the effects of a 20 Hz sinusoidal electromagnetic field (EMF; 6 mT and 113 mV/cm max) on collagen type I mRNA expression and extracellular matrix formation in comparison with the effects of growth factors. The cells were isolated from trabecular bone of a healthy individual (HO-197) and from a patient presenting with myositis ossificans (MO-192) and grown in a collagenous sponge-like substrate. Maximal enhancement of collagen type I expression after EMF treatment was 3.7-fold in HO-197 cells and 5.4-fold in MO-192 cells. Similar enhancement was found after transforming growth factor-beta (TGF-beta) and insulin-like growth factor-I (IGF-I) treatment. Combined treatment of the cells with EMF and the two growth factors TGF-beta and IGF-I did not act synergistically. MO-192 cells produced an osteoblast-characteristic extracellular matrix containing collagen type I, alkaline phosphatase, and osteocalcin, together with collagen type III, TP-1, and TP-3, two epitopes of an osteoblastic differentiation marker. The data suggest that the effects of EMFs on osteoblastic differentiation are comparable to those of TGF-beta and IGF-I. We conclude that EMF effects in the treatment of skeletal disorders and in orthopedic adjuvant therapy are mediated via enhancement of collagen type I mRNA expression, which may lead to extensive extracellular matrix synthesis.


Asunto(s)
Colágeno/biosíntesis , Colágeno/genética , Campos Electromagnéticos , Osteoblastos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Línea Celular , Terapia por Estimulación Eléctrica , Electrónica Médica/instrumentación , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Factor I del Crecimiento Similar a la Insulina/farmacología , Osteoblastos/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología
3.
J Virol ; 71(1): 645-9, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8985395

RESUMEN

Certain isolates of murine leukemia viruses (MuLVs) have, apart from a leukemogenic potential, the capability of inducing diseases of nonhematopoietic tissues in susceptible strains of mice. We have reported on the molecular cloning of a bone-tumorigenic virus, RFB-14 MuLV, which was found to induce benign bone tumors, osteomas, with 100% incidence in mice of the CBA/Ca strain (L. Pedersen, W. Behnisch, J. Schmidt, A. Luz, F. S. Pedersen, V. Erfle, and P. G. Strauss, J. Virol. 66:6186-6190, 1992). In order to analyze the bone tumor-inducing phenotype of RFB-14 MuLV, we have studied the pathogenic potential of recombinant viruses between RFB-14 and the nonosteomagenic, highly leukemogenic SL3-3 MuLV. The recombinants were constructed so as to reveal whether a major determinant of osteomagenicity maps to sequences within or outside the long terminal repeats (LTR). Our data show that a major determinant of the osteoma-inducing potential of RFB-14 MuLV maps to the non-LTR region of the genome. Furthermore, we demonstrate that a strong determinant of leukemogenicity is harbored by the non-LTR region of SL3-3 MuLV.


Asunto(s)
Mapeo Cromosómico , Genes Virales , Virus de la Leucemia Murina/genética , Osteoma/virología , Células 3T3 , Animales , Virus de la Leucemia Murina/patogenicidad , Linfoma/virología , Ratones , Ratones Endogámicos CBA , Recombinación Genética , Secuencias Repetitivas de Ácidos Nucleicos
4.
Virology ; 224(2): 533-8, 1996 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-8874513

RESUMEN

RFB virus is an ecotropic C-type retrovirus isolated from CF-1 mice, in which it is associated with induction of osteomas. Sequence analysis of the RFB provirus revealed no evidence for presence of an oncogene or a recombined env gene. RFB virus is a member of the murine leukemia virus (MuLV) group (RFB MuLV), sharing 97% nucleotide identity with the endogenous ecotropic provirus of AKR mice (Akv). Like Akv, expression of RFB MuLV mRNAs is inducible by dexamethasone treatment, indicating that FRB MuLV also shares transcriptional control signals with Akv. We assessed the pathogenic potential of RFB MuLV in NMRI mice, which, in contrast to CF-1 mice, do not contain endogenous ecotropic retroviruses. RFB MuLV induced osteomas, osteopetrosis, and lymphomas in newborn NMRI mice. Another CF-1 mouse-derived leukemia virus, FBJ MuLV, the helper virus of the FBJ osteosarcoma virus stock, as well as Akv, also induced osteomas, osteopetrosis, and lymphomas in NMRI mice similar to RFB MuLV. These findings indicate that endogenous retroviruses carry a pathogenic potential in hematopoietic tissues and in the skeleton.


Asunto(s)
Virus de la Leucemia Murina/genética , Virus de la Leucemia Murina/patogenicidad , Linfoma/virología , Oncogenes , Osteoma/virología , Osteopetrosis/virología , Animales , Transformación Celular Viral , Productos del Gen gag , Virus de la Leucemia Murina/metabolismo , Ratones , Datos de Secuencia Molecular , Mutación Puntual , Precursores de Proteínas , ARN Mensajero , ARN Viral
5.
Lab Invest ; 74(5): 895-906, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8642785

RESUMEN

Bone tissue formation and the expression of osteoblast-specific genes were compared in vitro and in vivo for two well characterized murine clonal osteosarcoma cell lines (K7 and K8). In vitro studies were carried out under conditions that promoted extracellular matrix morphogenesis and mineralization. The K8 cells showed 8-fold greater alkaline phosphatase activity and mineral accumulation than did K7 cells during 21 days of in vitro growth. The K8 cell line showed high levels of bone sialoprotein (BSP), collagen type I (COL I), and alkaline phosphatase (APase) mRNA expression throughout its growth in vitro. In contrast, K7 cells showed an almost complete absence of BSP and COL I and very low levels of APase throughout the culture period. In vitro, both cell lines expressed very low levels of osteocalcin (OC). For in vivo studies, we used a three-dimensional culture device that permitted analysis of tissue formation by the cells after their implantation into syngeneic mice. The K8 cells consistently generated extensive mineralized woven bone after their subcutaneous implantation. The striking features distinguishing the bone formed by the implanted cells from normal recipient bone were the complete absence of osteoclasts or matrix resorption, the absence of OC protein, and very low levels of OC mRNA expression in the tissues formed by these cell lines. BSP, APase, and COL I expressions were maintained at high levels in the K8-produced tissues. In contrast to their near absence in vitro, APase, BSP, and COL I were expressed by K7 cells and increased with time in vivo. These findings demonstrate that the K7 cells in vitro are less differentiated than K8 cells, but that K7 cells in vivo undergo osteogenic maturation. Thus, expression of bone-specific genes in these osteogenic cell lines was dependent on systemic or local factors in recipient animals and was distinct for these cell lines when grown under in vitro conditions. OC protein does not appear to be needed for the mineralization of the extracellular matrix but may be needed to provide the necessary signals for the resorption and remodeling of the tissue.


Asunto(s)
Neoplasias Óseas/metabolismo , Expresión Génica , Osteoblastos/citología , Osteogénesis , Osteosarcoma/metabolismo , Fosfatasa Alcalina/genética , Animales , Matriz Ósea/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Calcificación Fisiológica , Calcio/análisis , Colágeno/genética , Electroforesis en Gel de Agar , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Osteoblastos/metabolismo , Osteocalcina/análisis , Osteocalcina/genética , Osteopontina , Osteosarcoma/genética , Osteosarcoma/patología , ARN/análisis , ARN/genética , Sialoglicoproteínas/genética , Células Tumorales Cultivadas
6.
Cell Growth Differ ; 6(2): 171-7, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7756175

RESUMEN

The mouse T1 glycoprotein is a secreted molecule of the immunoglobulin superfamily with significant homology to interleukin 1 receptors. It is expressed during bone development, and the extracellular diffusible gene product is found associated with newly formed bone but not cartilage matrix. During osteogenic differentiation of mandibular condyles of newborn mice in vitro, T1 gene expression is induced shortly after cultivation and is observed throughout the differentiation process. The temporal expression pattern of the gene is an mandibular condyles indicates that T1 expression is an early marker of osteogenic differentiation. This view is substantiated by the analysis of T1 gene regulation in continuous osteogenic cell lines. Both in differentiating osteoblast-like KM-1K cells derived from mandibular condyles and in MC3T3 cells, T1 gene activity is preferentially associated with early differentiation stages. In mandibular condyles, the secreted extracellular T1 protein is deposited into newly formed osteoid but not into cartilage matrix. This novel bone matrix protein may locally modulate the availability of its ligand.


Asunto(s)
Matriz Ósea/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Cóndilo Mandibular/metabolismo , Proteínas de la Membrana , Proteínas/metabolismo , Receptores de Interleucina-1/metabolismo , Animales , Secuencia de Bases , Diferenciación Celular/genética , Línea Celular , Proteína 1 Similar al Receptor de Interleucina-1 , Cóndilo Mandibular/citología , Ratones , Datos de Secuencia Molecular , Osteogénesis/genética , ARN Mensajero/biosíntesis , Receptores de Interleucina , Homología de Secuencia de Aminoácido
7.
Virology ; 206(1): 85-92, 1995 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-7831844

RESUMEN

hMt-c-fos-LTR transgenic mice (U. Rüther, D. Komitowski, F. R. Schubert, and E. F. Wagner. Oncogene 4, 861-865, 1989) developed bone sarcomas in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. After infection of newborns with Akv, an infectious retrovirus derived from the ecotropic provirus of the AKR mouse, 69% (20/28) of female animals and 83% (24/29) of males developed malignant fibrous-osseous tumors. The tumors in infected transgenics developed with higher frequency and a 200-days shorter mean tumor latency period. The hMt-c-fos-LTR transgene was expressed in all the fibrous-osseous tumors. They also showed newly integrated Akv proviruses, but in most tumors Akv was detected and expressed in only a small number of the tumor cells. Wild-type C3H mice infected with Akv developed benign osteomas with an incidence of 33% and a latency period of 474 days. The data indicate that Akv exerts distinct pathogenic effects on the skeleton. In hMt-c-fos-LTR transgenic mice, predisposed to bone sarcomagenesis, Akv acts synergistically with the fos transgene, resulting in the development of fibrous-osseous tumors.


Asunto(s)
Virus de la Leucemia Murina AKR/patogenicidad , Neoplasias Óseas/virología , Genes fos , Sarcoma Experimental/virología , Infecciones Tumorales por Virus/virología , Animales , Secuencia de Bases , Neoplasias Óseas/genética , Cartilla de ADN , Femenino , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Transgénicos , Datos de Secuencia Molecular , Secuencias Repetitivas de Ácidos Nucleicos , Sarcoma Experimental/genética , Infecciones Tumorales por Virus/genética
8.
Virology ; 206(1): 93-9, 1995 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-7831845

RESUMEN

The contribution of endogenous retroviruses to the multistep process of lymphomagenesis was investigated in wild-type mice and in two different myc-kappa transgenic mouse lines by infection with Akv. This retrovirus is derived from the endogenous ecotropic provirus of the AKR mouse and was previously considered to be nonlymphomagenic. The mice of the two myc-k transgenic lines are predisposed to B-cell lymphomagenesis and were therefore considered to be more susceptible to Akv. For comparison, the same mouse strains were also infected with the exogenous Moloney murine leukemia virus (MoMuLV). Both MoMuLV and Akv increased the tumor incidence and shortened the tumor latency period in wild-type mice and in the transgenic mouse lines. The differences in pathogenicity, number of provirus integrations, and level of virus expression between MoMuLV and Akv indicate different mechanisms of lymphomagenesis: while MoMuLV induced tumors apparently by insertional mutagenesis involving common integration sites similar to previous reports, the enhancement of lymphomagenesis by Akv seems to be directed by other mechanisms.


Asunto(s)
Virus de la Leucemia Murina AKR/patogenicidad , Genes myc , Linfoma/virología , Infecciones Tumorales por Virus/virología , Animales , Linfocitos B/citología , Secuencia de Bases , Diferenciación Celular , Femenino , Reordenamiento Génico , Linfoma/genética , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Virus de la Leucemia Murina de Moloney/patogenicidad , Provirus/genética , Provirus/aislamiento & purificación , Linfocitos T/citología , Infecciones Tumorales por Virus/genética
9.
Virology ; 200(2): 837-41, 1994 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-8178469

RESUMEN

The mammalian genome harbors a large number of endogenous retroviruses and retrovirus-like elements. Increasing evidence is found that such elements can be activated and act as insertional mutagens. The activation of endogenous retroviral elements can be induced by a variety of environmental factors including irradiation. We have observed the insertion of a murine endogenous retrovirus-like ETn element into intro 4 of the p53 gene in an osteosarcoma cell line derived from a radiation-induced osteosarcoma. The insertion resulted in a p53-ETn-p53 fusion mRNA, a novel form of p53 mutation. This is the first report on insertion of an endogenous retroviral element into the p53 tumor suppressor gene. The data suggest that activated endogenous retroviruses and retrovirus-like elements might pose an enhanced risk for individuals exposed to noxae, which activate endogenous retroviral elements.


Asunto(s)
Elementos Transponibles de ADN/genética , Genes p53/genética , Mutagénesis Insercional , Osteosarcoma/genética , Retroviridae/genética , Animales , Secuencia de Bases , Genes p53/efectos de la radiación , Ratones , Datos de Secuencia Molecular , Osteosarcoma/etiología , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Células Tumorales Cultivadas
10.
Differentiation ; 56(1-2): 45-53, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8026646

RESUMEN

Xiphoids of newborn mice consist of young chondrogenic cells of primary cartilage. During in vitro cultivation, xiphoids showed, morphologically, characteristics of adipose differentiation. This process progressed with time and by day 21 of the culture most of the cells in the xiphoids represented morphological mature adipocytes. During this period, the level of mRNA of lipoprotein lipase, and adipocyte-characteristic gene, increased steadily, while the level of collagen type II mRNA decreased. Continuous DNA synthesis during the cultivation period, even in mature adipocytes confirmed the viability of the cells. Mandibular condyles of newborn mice obtain chondroprogenitor cells as well as young and mature chondroblasts and represent secondary cartilage. Under identical culture conditions mandibular condyles obtained from the same mice undergo osteogenic differentiation and form mature bone within 7 to 10 days. Common to both xiphoids and mandibular condyles is the capacity to transdifferentiate, but they show distinct, divergent differentiation pathways. These findings indicate that cartilagenous tissue of xiphoids undergoes transdifferentiation into adipose tissue in vitro.


Asunto(s)
Tejido Adiposo/citología , Cartílago/citología , Animales , Animales Recién Nacidos , Biomarcadores , Fenómenos Fisiológicos Sanguíneos , Diferenciación Celular , División Celular , Colágeno/metabolismo , Sondas de ADN , Regulación de la Expresión Génica , Lipoproteína Lipasa/metabolismo , Cóndilo Mandibular , Ratones , Ratones Endogámicos C3H , Técnicas de Cultivo de Órganos , Apófisis Xifoides
11.
Verh Dtsch Ges Pathol ; 78: 265-9, 1994.
Artículo en Alemán | MEDLINE | ID: mdl-7887031

RESUMEN

Newborn hMT-fos-LTR transgenic C3H mice and their non-transgenic siblings were infected with Akv, derived from the ecotropic provirus of the AKR mouse. Bone sarcomas in non-infected transgenics were observed in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of males at 523 days. Akv-infected transgenics developed bone tumors with higher frequency and at younger age: Females in 69% (20/28) at 268 +/- 122 days, males in 83% (24/29) at 279 +/- 109 days. In the majority of the bone tumors of Akv-infected transgenics (70% in females, 59% in males) cellular atypia was lacking and the histological pattern resembled human parosteal osteosarcoma. Only 50% (12/24) of bone tumors in Akv-infected transgenics revealed newly integrated virus sequences by Southern analysis. PCR analysis detected Akv sequences in DNAs of all tumors. Obviously, the insertion of Akv in a few cells induced the considerably accelerated bone tumor growth.


Asunto(s)
Neoplasias Óseas/fisiopatología , ADN Viral/análisis , Genes fos , Virus de la Leucemia Murina/patogenicidad , Animales , Animales Recién Nacidos , Neoplasias Óseas/patología , Neoplasias Óseas/virología , Femenino , Humanos , Virus de la Leucemia Murina/genética , Virus de la Leucemia Murina/aislamiento & purificación , Masculino , Metalotioneína/biosíntesis , Metalotioneína/genética , Ratones , Ratones Endogámicos AKR , Ratones Endogámicos C3H , Ratones Transgénicos , Osteosarcoma/patología , Osteosarcoma/fisiopatología , Osteosarcoma/virología , Reacción en Cadena de la Polimerasa
12.
J Virol ; 66(10): 6186-90, 1992 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1326664

RESUMEN

We report the molecular cloning of two replication-competent osteoma-inducing murine leukemia viruses from the RFB osteoma virus stock (M. P. Finkel, C. A. Reilly, Jr., B. O. Biskis, and I. L. Greco, p. 353-366, in C. H. G. Price and F. G. M. Ross, ed., Bone--Certain Aspects of Neoplasia, 1973). Like the original RFB osteoma virus stock, viruses derived from the molecular RFB clones induced multiple osteomas in mice of the CBA/Ca strain. The cloned RFB viruses were indistinguishable by restriction enzyme analysis and by nucleotide sequence analysis of their long-terminal-repeat regions and showed close relatedness to the Akv murine leukemia virus.


Asunto(s)
Clonación Molecular , Virus de la Leucemia Murina/genética , Osteoma/microbiología , Animales , Secuencia de Bases , ADN Viral , Virus de la Leucemia Murina/patogenicidad , Virus de la Leucemia Murina/fisiología , Ratones , Ratones Endogámicos CBA , Datos de Secuencia Molecular , Secuencias Repetitivas de Ácidos Nucleicos , Replicación Viral
13.
Int J Cancer ; 50(2): 252-8, 1992 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-1730519

RESUMEN

An important role for the p53 gene in osteogenic sarcomas has been imputed by identification of somatically acquired gene alterations in human osteosarcomas and by the development of osteosarcomas in p53 transgenic mice. To study the involvement of p53 in radiation-induced osteosarcomagenesis, we have investigated gene alterations and expression of p53 in radiation-induced murine osteosarcomas and tumor-derived cell lines. Eighteen of 31 tumors and 8 of 9 cells lines showed alterations in the p53 gene region, or elevated levels of p53 RNA. Expression of the osteoblast marker gene bone gla protein was substantially reduced in tumors which simultaneously showed high steady-state levels of p53 RNA. Our data indicate that p53, in addition to its function in regulating DNA synthesis, may be involved in the control of osteogenic differentiation in osteosarcomagenesis.


Asunto(s)
Expresión Génica/efectos de la radiación , Genes p53/genética , Neoplasias Inducidas por Radiación/genética , Osteosarcoma/genética , ARN Neoplásico/genética , Animales , Biomarcadores de Tumor/genética , Diferenciación Celular/fisiología , Genes p53/efectos de la radiación , Ratones , Ratones Endogámicos BALB C , Mutación , Trasplante de Neoplasias , Neoplasias Inducidas por Radiación/patología , Osteocalcina/genética , Osteosarcoma/etiología , Osteosarcoma/patología , ARN Neoplásico/efectos de la radiación , Células Tumorales Cultivadas
14.
Gene ; 103(2): 259-61, 1991 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-1889751

RESUMEN

Cathepsin B-encoding cDNA (CTSB) clones have been isolated from a lambda gt10 library of a murine osteosarcoma by differential screening during a search for genes which are typically expressed during osteogenic differentiation in mouse mandibular condyles in vitro. Sequencing of the CTSB 3' end revealed that the isolated sequence contained an 825-bp 3'-noncoding region, the polyadenylation signal and the poly(A) tail. The enhanced CTSB expression during the early stages of the enchondral ossification-like process in mandibular condyles in vitro suggests that CTSB participates in the degradation of cartilage matrix prior to the synthesis of bone matrix proteins.


Asunto(s)
Catepsina B/genética , Diferenciación Celular/fisiología , Expresión Génica/fisiología , Osteogénesis/fisiología , Animales , Secuencia de Bases , Humanos , Ratones , Datos de Secuencia Molecular , Poli A/genética , Ratas , Mapeo Restrictivo , Alineación de Secuencia , Células Tumorales Cultivadas
15.
Radiat Environ Biophys ; 30(3): 225-7, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1924711

RESUMEN

Temporally-limited internal irradiation after incorporation of short-lived bone-seeking radionuclides is a useful experimental tool for the investigation of extrinsic and intrinsic factors which modify the dose dependence of bone tumor risk. Here we describe some of the results obtained in experiments with female mice (mainly NMRI). The future aim of such experiments should be the prediction of risk of late effects using early molecular-biological changes. Molecular-biological descriptions in our model are at present very limited.


Asunto(s)
Neoplasias Óseas/etiología , Neoplasias Inducidas por Radiación/etiología , Animales , Lutecio , Ratones , Radio (Elemento) , Torio
16.
Virology ; 179(2): 931-5, 1990 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2173270

RESUMEN

N-tropic murine leukemia viruses have been observed in connection with radiation-induced osteosarcomagenesis in BALB/c mice. We have investigated the bone disease-inducing potential of molecularly cloned, BALB/c-derived N-tropic viruses in the random-bred NMRI mouse strain. The germ-line virus and an exogenous virus isolate were found to induce high incidences of osteopetrosis and lymphomas and a lower incidence of osteomas. Two viruses derived from somatically acquired proviruses of independent radiation-induced osteosarcomas induced lower incidence of osteopetrosis and lymphomas. Nucleotide sequence analysis of the long terminal repeat regions and RNase T1 fingerprint analysis revealed only few differences between the isolates. The possible involvement of N-tropic murine leukemia viruses in radiation-induced osteosarcomagenesis in the BALB/c mouse strain is discussed.


Asunto(s)
Virus de la Leucemia Murina/patogenicidad , Ratones Endogámicos BALB C/microbiología , Animales , Secuencia de Bases , Clonación Molecular , Virus de la Leucemia Murina/genética , Ratones , Mapeo Nucleótido , Osteosarcoma/microbiología , ARN Viral/química , Sarcoma Experimental/microbiología
17.
Onkologie ; 13(6): 405-14, 1990 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2092276

RESUMEN

Retroviruses first attracted attention as the etiological agents of tumors in various animals, including birds, rodents and primates. The retrovirus-induced tumors comprise above all T- and B-cell leukemias/lymphomas, chronic myelogenous leukemia and mammary carcinomas, and are characterized by a long latent period between infection and manifestation of the disease. Since their detection, oncogenic retroviruses have been the object of intense study contributing to our knowledge of basic mechanisms and molecular events involved in carcinogenesis in general. An essential step in the retrovirus life cycle is the covalent integration of the double-stranded DNA copy of viral RNA into the cellular genome, forming the provirus. The proviruses are quite stable and are generally a permanent acquisition for the cellular genome. Therefore, the presence of the provirus can have profound genetic implications for the host cell. There are at least three main routes that are assumed to lead to retroviral oncogenesis: Transduction of cell-derived oncogenes (v-onc) carried by some retroviruses, activation of cellular proto-oncogenes (c-onc) in cis by insertional mutation or activation of cellular genes in trans by virus encoded transcription factors.


Asunto(s)
Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Regulación Viral de la Expresión Génica/fisiología , Retroviridae/genética , Infecciones Tumorales por Virus/genética , Animales , Humanos , Mutagénesis Insercional/genética , Activación Transcripcional/genética , Transducción Genética/genética
18.
J Cell Biol ; 111(3): 1313-23, 1990 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2118143

RESUMEN

We have investigated the temporal pattern of expression of c-fos in cartilage cells in mouse mandibular condyles. During in vitro cultivation, the progenitor cells in this organ differentiate to osteoblasts, and hypertrophic chondrocytes start to show features indicative of osteogenic differentiation. Prior to these processes we observed two distinct patterns of c-fos expression. High, transient c-fos expression was found in the entire tissue within 30 min of culture. This type of c-fos expression appeared to result from mechanical forces applied during dissection. The second type of c-fos expression appeared in individual cells in the zone of hypertrophic chondrocytes. A varying number of formerly quiescent chondrocytes expressed high levels of c-fos mRNA after between 30 min and 10 d in culture, with a peak in the number of cells between days 1 and 3. c-fos expression in these cartilage cells was followed by DNA replication and expression of genes typifying osteoblastic differentiation. After 7 d in culture, groups of cells with the typical ultrastructural features of osteoblasts, and surrounded by an osteoid-like matrix, were observed in single chondrocyte-type lacunae, suggesting division of chondrocytes and differentiation to osteoblasts. The data suggest that c-fos may play a crucial role in the perturbation of determined pathways of skeletoblast differentiation and in the regulation of endochondral bone formation.


Asunto(s)
Cartílago/citología , Osteogénesis/genética , Proteínas Proto-Oncogénicas/biosíntesis , Animales , Autorradiografía , Diferenciación Celular/genética , División Celular , Colágeno/genética , Regulación de la Expresión Génica , Técnicas In Vitro , Ratones , Hibridación de Ácido Nucleico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-fos , Proteínas Proto-Oncogénicas c-myc , ARN Mensajero/análisis , Factores de Tiempo
19.
Differentiation ; 44(2): 122-31, 1990 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2178137

RESUMEN

Osteogenic tumours from c-fos (MT-c-fos-LTR)-transgenic mice and from mice infected with the v-fos-bearing FBR murine osteosarcoma virus (FBR MSV) showed close morphological and neoplastic similarities. Fos mRNA expression was elevated in both types of tumours, and expression of several genes characteristic of differentiated bone cells was either lower, enhanced, or not detectable in comparison to that in normal bone. Tumour-derived cell lines showed variable levels of exogenous fos expression; bone-cell-specific genes were similarly expressed in both primary tumours and tumour-derived cell lines. Upon transplantation the tumour cells formed fibrosarcomas, some of which contained areas of focal osseochondrous differentiation. Non-tumorigenic cell lines established from bone tissue of normal and MT-c-fos-LTR transgenic mice showed osteoblastic characteristics, whereas no parathyroid hormone (PTH) response was observed in transgenic tumour cell lines in spite of high alkaline phosphatase activity. These data indicate that deregulated fos expression interferes with terminal osteogenic differentiation in v-fos- and c-fos-induced bone tumours.


Asunto(s)
Neoplasias Óseas/inducido químicamente , Transformación Celular Neoplásica/efectos de los fármacos , Osteosarcoma/inducido químicamente , Proteínas Proto-Oncogénicas/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Desarrollo Óseo/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , AMP Cíclico/metabolismo , Expresión Génica , Ratones , Ratones Transgénicos , Oncogenes/genética , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/patología , Hormona Paratiroidea/farmacología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-fos
20.
Cancer Genet Cytogenet ; 47(2): 219-25, 1990 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-2357696

RESUMEN

A "masked" Philadelphia chromosome (Ph), t(1;22;9)(p32;q11;q34), was found in the bone marrow and peripheral blood cells of a patient with chronic myeloid leukemia (CML) during the chronic and blastic phases of the disease. As an additional change, a reciprocal translocation t(12;13)(p13;q14) was observed in the blastic phase. Southern blot analysis showed a rearrangement of the breakpoint cluster region (bcr). Northern blot analysis with a c-abl probe showed an abnormal 8.5 kb c-abl RNA transcript in addition to the normal 6- and 7-kilobase (kb) c-abl species. Thus, the results demonstrate the presence of a c-abl/bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t(9;22)(q34;q11) of CML.


Asunto(s)
Crisis Blástica/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Cromosoma Filadelfia , Crisis Blástica/patología , Northern Blotting , Southern Blotting , ADN de Neoplasias/genética , Femenino , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Persona de Mediana Edad , ARN Neoplásico/genética , Mapeo Restrictivo
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