A role for epidermal growth factor receptor, c-Src and focal adhesion kinase in an in vitro model for the progression of colon cancer

V G Brunton, B W Ozanne, C Paraskeva, M C Frame

Research output: Contribution to journalArticlepeer-review

Abstract

We have examined the function of the epidermal growth factor (EGF) receptor, c-Src and focal adhesion kinase (FAK) in the progression of colon cancer using an in vitro progression model. A non-tumorigenic cell line was derived from a premalignant colonic adenoma (PC/AA) from which a clonogenic variant was established (AA/C1). Following sequential treatment with sodium butyrate and the carcinogen N-methyl-N'-nitro-N-nitro-soguanidine an anchorage-independent line was isolated which, with time in culture, became tumorigenic when injected into athymic nude mice (AA/C1/SB10). We have shown that both EGF receptor and FAK protein levels were elevated in the carcinoma cells as compared to the adenoma cells, while the expression and activity of c-Src were unaltered during the adenoma to carcinoma transition. EGF induced the movement of the carcinoma cells into a reconstituted basement membrane which was not seen with the premalignant adenoma cells. This increased motility was accompanied by an EGF-induced increase in c-Src kinase activity, relocalisation of c-Src to the cell periphery and phosphorylation of FAK in the carcinoma cells but not in the adenoma cells. This suggests that c-Src plays a role in the biological behaviour of colonic carcinoma cells induced by migratory factors such as EGF, perhaps acting in conjunction with FAK to regulate focal adhesion turnover and tumour cell motility. Furthermore, although c-Src has been implicated in colonic tumour progression, we demonstrate here that in the adenoma to carcinoma in vitro model c-Src is not the driving force for this progression but co-operates with other molecules in carcinoma development.
Original languageEnglish
Pages (from-to)283-93
Number of pages11
JournalOncogene
Volume14
Issue number3
DOIs
Publication statusPublished - 23 Jan 1997

Keywords

  • Adenoma
  • Animals
  • Cell Adhesion Molecules
  • Cell Division
  • Cell Movement
  • Collagen
  • Colonic Neoplasms
  • Disease Progression
  • Drug Combinations
  • Epidermal Growth Factor
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Laminin
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Proteins
  • Phenotype
  • Protein-Tyrosine Kinases
  • Proteoglycans
  • Receptor, Epidermal Growth Factor
  • Tumor Cells, Cultured
  • src-Family Kinases

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