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, Panagiotis Z Anastasiadis, Zoran Gatalica, E Aubrey Thompson, Alan P Fields

Research output: Contribution to journalArticle

113 Citations (Scopus)

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

Fingerprint

Protein Kinase C
Colon
Carcinogenesis
Carcinogens
Phosphotransferases
Epithelial Cells
ras Proteins
Growth
Transgenic Mice
Epithelium

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo. / Murray, Nicole R; Jamieson, Lee; Yu, Wangsheng; Zhang, Jie; Gökmen-Polar, Yesim; Sier, Deborah; Anastasiadis, Panagiotis Z; Gatalica, Zoran; Thompson, E Aubrey; Fields, Alan P.

In: Journal of Cell Biology, Vol. 164, No. 6, 15.03.2004, p. 797-802.

Research output: Contribution to journalArticle

Murray, Nicole R ; Jamieson, Lee ; Yu, Wangsheng ; Zhang, Jie ; Gökmen-Polar, Yesim ; Sier, Deborah ; Anastasiadis, Panagiotis Z ; Gatalica, Zoran ; Thompson, E Aubrey ; Fields, Alan P. / Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo. In: Journal of Cell Biology. 2004 ; Vol. 164, No. 6. pp. 797-802.
@article{740e14388a6a4ae8aac1601359ad8653,
title = "Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo",
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.",
keywords = "Cell invasion, Rac1, Rat intestinal epithelial cells, Soft agar growth, Transgenic mice",
author = "Murray, {Nicole R} and Lee Jamieson and Wangsheng Yu and Jie Zhang and Yesim G{\"o}kmen-Polar and Deborah Sier and Anastasiadis, {Panagiotis Z} and Zoran Gatalica and Thompson, {E Aubrey} and Fields, {Alan P}",
year = "2004",
month = "3",
day = "15",
doi = "10.1083/jcb.200311011",
language = "English (US)",
volume = "164",
pages = "797--802",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo

AU - Murray, Nicole R

AU - Jamieson, Lee

AU - Yu, Wangsheng

AU - Zhang, Jie

AU - Gökmen-Polar, Yesim

AU - Sier, Deborah

AU - Anastasiadis, Panagiotis Z

AU - Gatalica, Zoran

AU - Thompson, E Aubrey

AU - Fields, Alan P

PY - 2004/3/15

Y1 - 2004/3/15

N2 - 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.

AB - 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.

KW - Cell invasion

KW - Rac1

KW - Rat intestinal epithelial cells

KW - Soft agar growth

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=4444221607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444221607&partnerID=8YFLogxK

U2 - 10.1083/jcb.200311011

DO - 10.1083/jcb.200311011

M3 - Article

C2 - 15024028

AN - SCOPUS:4444221607

VL - 164

SP - 797

EP - 802

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -