Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo

Nicole R. Murray, Lee Jamieson, Wangsheng Yu, Jie Zhang, Yesim Gökmen-Polar, Deborah Sier, Panos Anastasiadis, Zoran Gatalica, E. Aubrey Thompson, Alan P. Fields

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Abstract

Protein kinase C ι (PKCι) has been implicated in Ras signaling, however, a role for PKCι in oncogenic Ras-mediated transformation has not been established. Here, we show that PKCι is a critical downstream effector of oncogenic Ras in the colonic epithelium. Transgenic mice expressing constitutively active PKCι in the colon are highly susceptible to carcinogen-induced colon carcinogenesis, whereas mice expressing kinase-deficient PKCι (kdPKCι) are resistant to both carcinogen- and oncogenic Ras-mediated carcinogenesis. Expression of kdPKCι in Ras-transformed rat intestinal epithelial cells blocks oncogenic Ras-mediated activation of Rac1, cellular invasion, and anchorage-independent growth. Constitutively active Rac1 (RacV12) restores invasiveness and anchorage-independent growth in Ras-transformed rat intestinal epithelial cells expressing kdPKCι. Our data demonstrate that PKCι is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCι, and Rac1.

Original languageEnglish (US)
Pages (from-to)797-802
Number of pages6
JournalJournal of Cell Biology
Volume164
Issue number6
DOIs
StatePublished - Mar 15 2004

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Keywords

  • Cell invasion
  • Rac1
  • Rat intestinal epithelial cells
  • Soft agar growth
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology

Cite this

Murray, N. R., Jamieson, L., Yu, W., Zhang, J., Gökmen-Polar, Y., Sier, D., Anastasiadis, P., Gatalica, Z., Thompson, E. A., & Fields, A. P. (2004). Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo. Journal of Cell Biology, 164(6), 797-802. https://doi.org/10.1083/jcb.200311011