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

S. Empereur, S. Djelloul, Y. Di Gioia, E. Bruyneel, M. Mareel, J. Van Hengel, F. Van Roy, P. Comoglio, Sara Courtneidge, C. Paraskeva, E. Chastre, C. Gespach

Research output: Contribution to journalArticle

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Abstract

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 pp60(sc) 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.

Original languageEnglish (US)
Pages (from-to)241-250
Number of pages10
JournalBritish Journal of Cancer
Volume75
Issue number2
StatePublished - 1997
Externally publishedYes

Fingerprint

Adenomatous Polyposis Coli
Hepatocyte Growth Factor
Oncogenes
Adenoma
Cadherins
Epithelial Cells
Proto-Oncogene Proteins c-met
Carcinoma
Cell Line
Catenins
src-Family Kinases
Oncogene Proteins
Cell Adhesion Molecules
Southern Blotting
Tumor Suppressor Genes
Protein-Tyrosine Kinases
Colonic Neoplasms
Reverse Transcription
Cell Differentiation
Colon

Keywords

  • APC
  • Cadherin
  • Catenins
  • Hepatocyte growth factor
  • Intestinal cell differentiation
  • p120(cas-)

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Empereur, S.; Djelloul, S.; Di Gioia, Y.; Bruyneel, E.; Mareel, M.; Van Hengel, J.; Van Roy, F.; Comoglio, P.; Courtneidge, Sara; Paraskeva, C.; Chastre, E.; Gespach, C.

In: British Journal of Cancer, Vol. 75, No. 2, 1997, p. 241-250.

Research output: Contribution to journalArticle

Empereur, S, Djelloul, S, Di Gioia, Y, Bruyneel, E, Mareel, M, Van Hengel, J, Van Roy, F, Comoglio, P, Courtneidge, S, Paraskeva, C, Chastre, E & Gespach, C 1997, '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', British Journal of Cancer, vol. 75, no. 2, pp. 241-250.
Empereur, S. ; Djelloul, S. ; Di Gioia, Y. ; Bruyneel, E. ; Mareel, M. ; Van Hengel, J. ; Van Roy, F. ; Comoglio, P. ; Courtneidge, Sara ; Paraskeva, C. ; Chastre, E. ; Gespach, C. / 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. In: British Journal of Cancer. 1997 ; Vol. 75, No. 2. pp. 241-250.
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abstract = "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 pp60(sc) 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.",
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AU - Mareel, M.

AU - Van Hengel, J.

AU - Van Roy, F.

AU - Comoglio, P.

AU - Courtneidge, Sara

AU - Paraskeva, C.

AU - Chastre, E.

AU - Gespach, C.

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