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1.
Pathology ; 33(1): 73-84, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11280614

RESUMO

The critical role of TGFbeta in development and growth control is well established but the signalling pathway has only recently been elucidated. Identification of the Smads as TGFbeta's intracellular signalling mediators has led to an explosion of information on a novel signalling network that links the cell surface to the nucleus. Many cancers develop resistance to the growth-inhibitory effects of TGFbeta and mutations in signalling pathway components have been discovered that may underly tumour progression.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Transativadores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Humanos , Modelos Biológicos , Proteína Smad2 , Proteína Smad3 , Proteína Smad4
2.
Leukemia ; 13(4): 535-41, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10214859

RESUMO

Genomic instability is one mechanism proposed to play a role in the disease progression of chronic myeloid leukemia (CML). Microsatellite regions in the type II transforming growth factor-beta receptor (TGF-beta RII) gene appear to be targets for mutation in some cancers displaying microsatellite instability (replication error phenotype, RER+). Furthermore, TGF-beta RII mutations in RER+ tumors have been associated with decreased TGF-beta RII mRNA levels. As TGF-beta is a potent negative growth regulator of hematopoietic cells, investigations were undertaken to determine whether inactivation of the receptor by microsatellite alteration might be involved in the progression of CML. Analysis of TGF-beta RII mRNA expression by RNase protection, with comparison of cells from the chronic, accelerated and blast phases of CML, showed no change in TGF-beta RII transcript levels during disease progression. However, during each phase of the disease, low levels of TGF-beta RII were detected when compared with the hematopoietic cells of normal donors. Furthermore, this decreased expression was also observed in the other myeloproliferative disorders, polycythemia rubra vera (PRV) and essential thrombocythemia (ET). The leukemia cell lines K562 and HL-60 had no detectable TGF-beta RII mRNA. Two microsatellite regions found altered in RER+ colon cancers were analyzed to establish if these sequences were aberrant in CML. No alteration was detected in either of these regions in any phase of the disease. These results suggest that alterations of the microsatellite regions in the TGF-beta RII gene are not involved in the progression of CML. Decreased expression of TGF-beta RII in CML cells and leukemia cell lines raises the possibility that altered expression of the receptor may play a role in the initiation and/or maintenance of the disease state.


Assuntos
Pareamento Incorreto de Bases , Reparo do DNA , DNA de Neoplasias/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Repetições de Microssatélites , Receptores de Fatores de Crescimento Transformadores beta/genética , Crise Blástica/genética , Crise Blástica/patologia , Neoplasias do Colo/genética , Progressão da Doença , Regulação Leucêmica da Expressão Gênica , Genes , Células HL-60/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Células Jurkat/metabolismo , Células K562/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide de Fase Acelerada/genética , Leucemia Mieloide de Fase Acelerada/patologia , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/patologia , Policitemia Vera/genética , Policitemia Vera/patologia , Proteínas Serina-Treonina Quinases , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Receptor do Fator de Crescimento Transformador beta Tipo II , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologia , Células Tumorais Cultivadas
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