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1.
Adv Physiol Educ ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38932697

RESUMO

Much of the research about STEM students' motivation measures the relationship between student motivation and academic outcomes, focusing on the student's mindset. This study takes a different approach, considering student motivation and instructional practices. Teaching practices and student motivation were analyzed simultaneously in undergraduate Biology classes using a self-determination theory-based survey and the Classroom Observation Protocol for Undergraduate STEM, and observation notes were collected to document instructor and student behaviors. Quantitative data was used to differentiate students' motivational levels and qualitative data was collected to describe how instructors use specific teaching practices. The results provide a lens into how students' intrinsic motivation varies alongside the instructional practices and interactions in these classes. We found a correlation between higher levels of student motivation in interactive lecture and student-centered teaching profiles. This study highlights how the same practice can be implemented by multiple instructors with varying student motivation scores, pointing out the importance of fidelity to evidence-based instructional practice methods. The results of this study are discussed in the context of published empirical studies examining evidence-based instructional practices that are conceptually supportive of autonomy, competence, and relatedness. Active learning practices observed in this study correlated to positive learning outcomes are discussed and may serve as a guide for instructors interested in implementing specific active learning practices. Recommendations for instructors and departments that are interested in flexible methods to monitor progress toward active learning practices in biology and other STEM disciplines by combining the COPUS and self-determination survey results are presented.

2.
Oncogene ; 42(10): 737-747, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36604566

RESUMO

Inter-patient and intra-tumoral heterogeneity complicate the identification of predictive biomarkers and effective treatments for basal triple negative breast cancer (b-TNBC). Invasion is the initiating event in metastasis and can occur by both collective and single-cell mechanisms. We cultured primary organoids from a b-TNBC genetically engineered mouse model in 3D collagen gels to characterize their invasive behavior. We observed that organoids from the same tumor presented different phenotypes that we classified as non-invasive, collective and disseminative. To identify molecular regulators driving these invasive phenotypes, we developed a workflow to isolate individual organoids from the collagen gels based on invasive morphology and perform RNA sequencing. We next tested the requirement of differentially regulated genes for invasion using shRNA knock-down. Strikingly, KRAS was required for both collective and disseminative phenotypes. We then performed a drug screen targeting signaling nodes upstream and downstream of KRAS. We found that inhibition of EGFR, MAPK/ERK, or PI3K/AKT signaling reduced invasion. Of these, ERK inhibition was striking for its ability to potently inhibit collective invasion and dissemination. We conclude that different cancer cells in the same b-TNBC tumor can express different metastatic molecular programs and identified KRAS and ERK as essential regulators of collective and single cell dissemination.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas p21(ras) , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética , Movimento Celular/genética
3.
Sci Transl Med ; 14(656): eabn7571, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921474

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model (GEMM), multiple patient-derived xenografts, and archival patient samples exhibited large populations in vivo of hybrid E/M cells that lead invasion ex vivo while expressing both epithelial and mesenchymal characteristics. The mesenchymal marker vimentin promoted invasion and repressed metastatic outgrowth. We next tested the requirement for five EMT transcription factors and observed distinct patterns of utilization during invasion and colony formation. These differences suggested a sequential activation of multiple EMT molecular programs during the metastatic cascade. Consistent with this model, our longitudinal single-cell RNA analysis detected three different EMT-related molecular patterns. We observed cancer cells progressing from epithelial to hybrid E/M and strongly mesenchymal patterns during invasion and from epithelial to a hybrid E/M pattern during colony formation. We next investigated the relative epithelial versus mesenchymal state of cancer cells in both GEMM and patient metastases. In both contexts, we observed heterogeneity between and within metastases in the same individual. We observed a complex spectrum of epithelial, hybrid E/M, and mesenchymal cell states within metastases, suggesting that there are multiple successful molecular strategies for distant organ colonization. Together, our results demonstrate an important and complex role for EMT programs during TNBC metastasis.


Assuntos
Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Humanos , Camundongos , Metástase Neoplásica , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Vimentina
5.
Cell Metab ; 33(7): 1342-1357.e10, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34102109

RESUMO

Mechanical signals from the tumor microenvironment modulate cell mechanics and influence cell metabolism to promote cancer aggressiveness. Cells withstand external forces by adjusting the stiffness of their cytoskeleton. Microtubules (MTs) act as compression-bearing elements. Yet how cancer cells regulate MT dynamic in response to the locally constrained environment has remained unclear. Using breast cancer as a model of a disease in which mechanical signaling promotes disease progression, we show that matrix stiffening rewires glutamine metabolism to promote MT glutamylation and force MT stabilization, thereby promoting cell invasion. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, decreased MT glutamylation by overexpressing tubulin mutants lacking glutamylation site(s) decreased MT stability, thereby hampering cancer aggressiveness in vitro and in vivo. Together, our results decipher part of the enigmatic tubulin code that coordinates the fine-tunable properties of MT and link cell metabolism to MT dynamics and cancer aggressiveness.


Assuntos
Ácido Glutâmico/metabolismo , Mecanotransdução Celular/fisiologia , Microtúbulos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Células Cultivadas , Metabolismo Energético/fisiologia , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Processamento de Proteína Pós-Traducional , Tubulina (Proteína)/metabolismo , Microambiente Tumoral/fisiologia
6.
Cancers (Basel) ; 13(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578855

RESUMO

Neuroblastoma is a paediatric malignancy of the developing sympathetic nervous system. About half of the patients have metastatic disease at the time of diagnosis and a survival rate of less than 50%. Our understanding of the cellular processes promoting neuroblastoma metastases will be facilitated by the development of appropriate experimental models. In this study, we aimed to explore the invasion of neuroblastoma cells and organoids from patient-derived xenografts (PDXs) grown embedded in 3D extracellular matrix (ECM) hydrogels by time-lapse microscopy and quantitative image analysis. We found that the ECM composition influenced the growth, viability and local invasion of organoids. The ECM compositions induced distinct cell behaviours, with Matrigel being the preferred substratum for local organoid invasion. Organoid invasion was cell line- and PDX-dependent. We identified six distinct phenotypes in PDX-derived organoids. In contrast, NB cell lines were more phenotypically restricted in their invasion strategies, as organoids isolated from cell line-derived xenografts displayed a broader range of phenotypes compared to clonal cell line clusters. The addition of FBS and bFGF induced more aggressive cell behaviour and a broader range of phenotypes. In contrast, the repression of the prognostic neuroblastoma marker, MYCN, resulted in less aggressive cell behaviour. The combination of PDX organoids, real-time imaging and the novel 3D culture assays developed herein will enable rapid progress in elucidating the molecular mechanisms that control neuroblastoma invasion.

8.
Am J Pathol ; 188(9): 2074-2086, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30126548

RESUMO

The gene leukocyte-specific protein-1 (LSP1), encodes an F-actin binding protein that directly interacts with the mitogen-activated protein kinase pathway. LSP1 has copy number variations in 52% of human hepatocellular carcinoma (HCC). LSP1 suppresses proliferation and migration in hepatocytes. LSP1 binds to the rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein/extracellular signal-regulated kinase (ERK)/ERK signaling cassette, the target for sorafenib, a crucial chemotherapeutic agent for HCC. This study addresses the role of LSP1 in liver regeneration and sensitivity to sorafenib in normal and neoplastic hepatocytes. Two mouse models, an Lsp1 global knockout (LSP1KO) and a hepatocyte-specific Lsp1 transgenic (LSP1TG) mouse, were used. After two-thirds hepatectomy (PHx), LSP1KO mice displayed increased proliferation and ERK activation, whereas LSP1TG mice displayed suppressed proliferation and decreased ERK activation. LSP1KO hepatocytes cultured without growth factors exhibited increased proliferation, whereas LSP1TG hepatocytes showed decreased proliferation. Rat and human hepatoma cells expressing Lsp1 shRNA displayed increased sensitivity to sorafenib, as evidenced by decreased cell numbers and phosphorylated ERK expression compared with control. LSP1 KO mice treated with sorafenib before PHx displayed decreased hepatocyte proliferation. Our data show that loss of LSP1 function, observed in HCC, leads to increased sensitivity to sorafenib treatment and enhanced hepatocellular proliferation after PHx in vivo and in cultured cells.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Resistência a Medicamentos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Sorafenibe/farmacologia , Animais , Antineoplásicos/farmacologia , Proliferação de Células , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Regeneração Hepática/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos , Fosforilação
9.
Contraception ; 96(4): 261, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28716468
11.
Contraception ; 95(2): 190-197, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27621043

RESUMO

OBJECTIVES: Clinicians and researchers need an accurate tool assessing contraceptive knowledge in order to understand the effectiveness of teaching efforts. However, most widely used indices are outdated. The objective of this study is to create an evidence-based assessment tool and determine its validity and reliability for measuring contraceptive knowledge. STUDY DESIGN: The study team developed the 25-question multiple-choice tool entitled the Contraceptive Knowledge Assessment (CKA). Expert reviewers examined content validity and semistructured patient interviews acquired feedback on subject matter and comprehension. A two-tiered approach explored criterion validity via (1) comparison with the gold standard (Contraceptive Knowledge Inventory) and (2) comparison between groups with lower and higher contraceptive knowledge. Repeat testing after 2-4 weeks evaluated test-retest reliability. RESULTS: Six experts and seven patients provided feedback on the initial CKA. One hundred two reproductive-aged male and female patients and 27 medical students completed the final CKA with an overall mean patient score of 9/25 (36%). The mean score on the CKA was higher than the mean score on the gold standard (9.1 vs. 5.8, p<.001). Patients scored lower on the CKA than did medical students (9.1 [36.4%] vs.19.4 [77.6%], p<.005). There were no differences within patients' results with repeat testing over time (p=.667). CONCLUSIONS: The CKA is a valid and reliable tool to measure a patient's level of knowledge regarding contraception. This research tool may allow for the assessment of baseline knowledge, educational gaps, and improvement after an intervention. Knowledge may be lower than previous studies suggest, signifying need for improved education on contraception and better understanding of the relationship between knowledge and behavior change. IMPLICATIONS: The CKA provides an evidence-based, reliable, and validated assessment of contraceptive knowledge. This modern tool may help to determine the effectiveness of interventions to improve education on contraception.


Assuntos
Anticoncepção , Avaliação Educacional/métodos , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Anticoncepção/métodos , Comportamento Contraceptivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Inquéritos e Questionários , Adulto Jovem
12.
Hepatology ; 64(5): 1711-1724, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27397846

RESUMO

Receptor tyrosine kinases MET and epidermal growth factor receptor (EGFR) are critically involved in initiation of liver regeneration. Other cytokines and signaling molecules also participate in the early part of the process. Regeneration employs effective redundancy schemes to compensate for the missing signals. Elimination of any single extracellular signaling pathway only delays but does not abolish the process. Our present study, however, shows that combined systemic elimination of MET and EGFR signaling (MET knockout + EGFR-inhibited mice) abolishes liver regeneration, prevents restoration of liver mass, and leads to liver decompensation. MET knockout or simply EGFR-inhibited mice had distinct and signaling-specific alterations in Ser/Thr phosphorylation of mammalian target of rapamycin, AKT, extracellular signal-regulated kinases 1/2, phosphatase and tensin homolog, adenosine monophosphate-activated protein kinase α, etc. In the combined MET and EGFR signaling elimination of MET knockout + EGFR-inhibited mice, however, alterations dependent on either MET or EGFR combined to create shutdown of many programs vital to hepatocytes. These included decrease in expression of enzymes related to fatty acid metabolism, urea cycle, cell replication, and mitochondrial functions and increase in expression of glycolysis enzymes. There was, however, increased expression of genes of plasma proteins. Hepatocyte average volume decreased to 35% of control, with a proportional decrease in the dimensions of the hepatic lobules. Mice died at 15-18 days after hepatectomy with ascites, increased plasma ammonia, and very small livers. CONCLUSION: MET and EGFR separately control many nonoverlapping signaling endpoints, allowing for compensation when only one of the signals is blocked, though the combined elimination of the signals is not tolerated; the results provide critical new information on interactive MET and EGFR signaling and the contribution of their combined absence to regeneration arrest and liver decompensation. (Hepatology 2016;64:1711-1724).


Assuntos
Receptores ErbB/fisiologia , Falência Hepática/etiologia , Regeneração Hepática/fisiologia , Proteínas Proto-Oncogênicas c-met/fisiologia , Animais , Masculino , Camundongos , Transdução de Sinais
13.
Am J Obstet Gynecol ; 214(6): 731.e1-731.e10, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26873276

RESUMO

BACKGROUND: Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. OBJECTIVES: The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. METHODS: This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. RESULTS: Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). CONCLUSIONS: Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/terapia , Miométrio/diagnóstico por imagem , Aborto Incompleto , Aborto Espontâneo , Adolescente , Adulto , Malformações Arteriovenosas/etiologia , Velocidade do Fluxo Sanguíneo , Transfusão de Sangue/estatística & dados numéricos , Cesárea/efeitos adversos , Curetagem/estatística & dados numéricos , Dilatação e Curetagem/efeitos adversos , Feminino , Humanos , Mola Hidatiforme/complicações , Histerectomia/estatística & dados numéricos , Metotrexato/uso terapêutico , Miométrio/irrigação sanguínea , Gravidez , Estudos Retrospectivos , Ultrassonografia Doppler em Cores , Embolização da Artéria Uterina/estatística & dados numéricos , Hemorragia Uterina/etiologia , Adulto Jovem
14.
PLoS One ; 9(4): e96053, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24763697

RESUMO

Exogenous interleukin 6 (IL-6), synthesized at the initiation of the acute phase response, is considered responsible for signaling hepatocytes to produce acute phase proteins. It is widely posited that IL-6 is either delivered to the liver in an endocrine fashion from immune cells at the site of injury, or alternatively, in a paracrine manner by hepatic immune cells within the liver. A recent publication showed there was a muted IL-6 response in lipopolysaccharide (LPS)-injured mice when nuclear NFκB was specifically inactivated in the hepatocytes. This indicates hepatocellular signaling is also involved in regulating the acute phase production of IL-6. Herein, we present extensive in vitro and in vivo evidence that normal hepatocytes are directly induced to synthesize IL-6 mRNAs and protein by challenge with LPS, a bacterial hepatotoxin, and by HGF, an important regulator of hepatic homeostasis. As the IL-6 receptor is found on the hepatocyte, these results reveal that induction of the acute phase response can be regulated in an autocrine as well as endocrine/paracrine fashion. Further, herein we provide data indicating that following partial hepatectomy (PHx), HGF differentially regulates IL-6 production in hepatocytes (induces) versus immune cells (suppresses), signifying disparate regulation of the cell sources involved in IL-6 production is a biologically relevant mechanism that has previously been overlooked. These findings have wide ranging ramifications regarding how we currently interpret a variety of in vivo and in vitro biological models involving elements of IL-6 signaling and the hepatic acute phase response.


Assuntos
Hepatócitos/metabolismo , Interleucina-6/biossíntese , Animais , Comunicação Autócrina , Células Cultivadas , Meios de Cultura Livres de Soro , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Hepatócitos/efeitos dos fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Ratos Endogâmicos F344
15.
Obstet Gynecol ; 123(2 Pt 2 Suppl 2): 450-453, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24413242

RESUMO

BACKGROUND: Ovarian vein thrombophlebitis is commonly considered to be a postpartum or postoperative disease. We describe an unusual case of ovarian vein thrombophlebitis in a nonpuerperal patient without recent surgery that was associated with venous compression by a large uterine myoma. CASE: A 32-year-old nulligravid woman presented with fever, leukocytosis, and severe abdominal pain. Ultrasound demonstrated an enlarged uterus measuring 16.6×7.9×9.6 cm with a dominant left exophytic myoma; computed tomography scan revealed an intraluminal thrombus in the left ovarian vein. The patient recovered with antibiotics and anticoagulation. Abdominal myomectomy was performed to remove the structural contributor for thrombosis formation. CONCLUSION: Ovarian vein thrombophlebitis should be considered in patients with abdominal pain, fever, and evidence of venous stasis, even if they are lacking typical risk factors of pregnancy or surgery.


Assuntos
Leiomioma/complicações , Ovário/irrigação sanguínea , Tromboflebite/etiologia , Neoplasias Uterinas/complicações , Adulto , Feminino , Humanos
16.
PLoS One ; 8(9): e74625, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24058607

RESUMO

Particularly interesting new cysteine-histidine-rich protein (PINCH) protein is part of the ternary complex known as the IPP (integrin linked kinase (ILK)-PINCH-Parvin-α) complex. PINCH itself binds to ILK and to another protein known as Rsu-1 (Ras suppressor 1). We generated PINCH 1 and PINCH 2 Double knockout mice (referred as PINCH DKO mice). PINCH2 elimination was systemic whereas PINCH1 elimination was targeted to hepatocytes. The genetically modified mice were born normal. The mice were sacrificed at different ages after birth. Soon after birth, they developed abnormal hepatic histology characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells and increased deposition of extracellular matrix. After a sustained and prolonged proliferation of all epithelial components, proliferation subsided and final liver weight by the end of 30 weeks in livers with PINCH DKO deficient hepatocytes was 40% larger than the control mice. The livers of the PINCH DKO mice were also very stiff due to increased ECM deposition throughout the liver, with no observed nodularity. Mice developed liver cancer by one year. These mice regenerated normally when subjected to 70% partial hepatectomy and did not show any termination defect. Ras suppressor 1 (Rsu-1) protein, the binding partner of PINCH is frequently deleted in human liver cancers. Rsu-1 expression is dramatically decreased in PINCH DKO mouse livers. Increased expression of Rsu-1 suppressed cell proliferation and migration in HCC cell lines. These changes were brought about not by affecting activation of Ras (as its name suggests) but by suppression of Ras downstream signaling via RhoGTPase proteins. In conclusion, our studies suggest that removal of PINCH results in enlargement of liver and tumorigenesis. Decreased levels of Rsu-1, a partner for PINCH and a protein often deleted in human liver cancer, may play an important role in the development of the observed phenotype.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Proteínas com Domínio LIM/metabolismo , Fígado/metabolismo , Fígado/patologia , Proteínas de Membrana/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Animais , Apoptose , Peso Corporal , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Regulação para Baixo , Matriz Extracelular/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Cinética , Proteínas com Domínio LIM/deficiência , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Regeneração Hepática , Proteínas de Membrana/deficiência , Camundongos , Camundongos Knockout , Modelos Biológicos , Tamanho do Órgão , Ratos , Transdução de Sinais , Regulação para Cima
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