Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion
| Autor: | S. Courtneidge, Sylvie Empereur, Paolo M. Comoglio, Marcus Mareel, Christian Gespach, S. Djelloul, E. A. Bruyneel, J. van Hengel, C Paraskeva, Eric Chastre, Y. Di Gioia, F. Van Roy |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Delta Catenin Adenomatous polyposis coli Cellular differentiation Antigens Polyomavirus Transforming Adenomatous Polyposis Coli Protein Transplantation Heterologous Mice Nude Transfection Mice medicine Animals Neoplasm Invasiveness Phosphorylation Autocrine signalling Phosphotyrosine biology Oncogene Hepatocyte Growth Factor Receptor Protein-Tyrosine Kinases Catenins DNA Neoplasm Oncogenes Proto-Oncogene Proteins c-met Cadherins Phosphoproteins Cytoskeletal Proteins Genes src Oncology Adenomatous Polyposis Coli Catenin biology.protein Cancer research Hepatocyte growth factor Collagen Tyrosine kinase Cell Adhesion Molecules Chickens Gels Neoplasm Transplantation alpha Catenin Proto-oncogene tyrosine-protein kinase Src medicine.drug Research Article Signal Transduction |
| Zdroj: | British Journal of Cancer Scopus-Elsevier |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp60src tyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 |
| Databáze: | OpenAIRE |
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