Met receptor overexpression and oncogenic Ki-ras mutation cooperate to enhance tumorigenicity of colon cancer cells in vivo

Isolde Seiden Long, Kathy Han, Ming Li, Senji Shirasawa, Takehiko Sasazuki, Michael Johnston, Ming Sound Tsao

研究成果: Contribution to journalArticle

37 被引用数 (Scopus)

抄録

We have investigated the influence of Ki-ras oncogene on Met/hepatocyte growth factor (HGF) receptor signaling in human carcinoma cells. The model system used in these studies included the DLD-1 colon cancer cell line with a mutated Ki-ras allele, and the DKO-4 cell line generated from DLD-1, with its mutant Ki-ras allele inactivated by targeted disruption. These cell lines were transduced with cDNAs of either active Met receptor or dominant negative Met receptor. As compared to the DLD-1 cells, constitutive overexpression of Met receptor in this cell line (DLD-1-Met) resulted in increased tumorigenicity in SCID mice. In contrast, overexpression of Met in DKO-4 cells (DKO-4-Met) that have lost oncogenic Ras activity demonstrated suppressed tumorigenicity with respect to the parent DKO-4 cell line. Tumors formed by the DLD-1-Met cells showed increased levels of mitogen-activated protein kinase (MAPK) and lower levels of apoptosis compared to the DKO-4-Met tumors. Overexpression of the dominant negative Met receptor cDNA decreased the Met phosphorylation levels in both DLD-1 and DKO-4 cells, but only suppressed tumorigenicity in the DKO-4 cell line. In vitro, HGF stimulation of DLD-1 cells resulted in a prolonged duration of MAPK activation, while DKO-4 cells exhibited a rapid attenuation of MAPK phosphorylation. The results suggest that Ki-ras mutations and HGF signaling cooperate to enhance tumor growth by increased duration of MAPK activation and decreased apoptosis in human carcinoma cells.

本文言語英語
ページ(範囲)393-401
ページ数9
ジャーナルMolecular Cancer Research
1
5
出版ステータス出版済み - 3 1 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Oncology
  • Cancer Research

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