Oncogenic ras modulates epidermal growth factor responsiveness in endometrial carcinomas

Kiyoko Kato, Y. Ueoka, K. Kato, T. Tamura, J. Nishida, N. Wake

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Since the majority of endometrial carcinomas do not contain any detectable ras mutations, the precise contribution of aberrant Ras function, if any, to endometrial carcinoma development remains to be determined. Since there is considerable evidence that Ras transformation is associated with a decreased requirement for growth factors, we compared the growth response of endometrial carcinoma cells harbouring wild-type (Ishikawa cells) or mutated (HHUA cells) K-ras to epidermal growth factor (EGF). K-ras mutation did not significantly affect the level of the EGF receptor (EGFR) expressed in these carcinoma cells. EGF could stimulate the growth of Ishikawa, but not HHUA cells. Furthermore, EGF caused elevation of Ras-GTP levels in Ishikawa, but not HHUA cells. However, the introduction of mutated, but not normal, K-ras into Ishikawa cells rendered them non-responsive to EGF growth stimulation. Thus, the presence of mutated K-ras alone modulated the growth response of endometrial carcinoma cells to EGF. An inhibitor of the EGFR tyrosine kinase activity could prevent soft agar colony formation of Ishikawa cells, but not HHUA or mutant K-ras(12v)-transfected Ishikawa cells. Taken together, these results suggest that mutated K-ras causes a loss of responsiveness to EGF stimulation and that EGFR function is dispensable for the growth of mutant Ras-positive endometrial carcinoma cells.

Original languageEnglish
Pages (from-to)737-744
Number of pages8
JournalEuropean Journal of Cancer
Volume34
Issue number5
DOIs
Publication statusPublished - Apr 1 1998

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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