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

Nicole R. Murray, Lee Jamieson, Wangsheng Yu, Jie Zhang, Yesim Polar, Deborah Sier, Panos 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
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

Murray, N. R., Jamieson, L., Yu, W., Zhang, J., Polar, Y., Sier, D., ... 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

Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo. / Murray, Nicole R.; Jamieson, Lee; Yu, Wangsheng; Zhang, Jie; Polar, Yesim; Sier, Deborah; Anastasiadis, Panos; 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, NR, Jamieson, L, Yu, W, Zhang, J, Polar, Y, Sier, D, Anastasiadis, P, Gatalica, Z, Thompson, EA & Fields, AP 2004, 'Protein kinase Cι is required for Ras transformation and colon carcinogenesis in vivo', Journal of Cell Biology, vol. 164, no. 6, pp. 797-802. https://doi.org/10.1083/jcb.200311011
Murray, Nicole R. ; Jamieson, Lee ; Yu, Wangsheng ; Zhang, Jie ; Polar, Yesim ; Sier, Deborah ; Anastasiadis, Panos ; 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{dc477050444b4e26b4eb0c1b7f92a832,
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 Polar and Deborah Sier and Panos Anastasiadis and Zoran Gatalica and Thompson, {E. Aubrey} and Fields, {Alan P.}",
year = "2004",
month = "3",
day = "15",
doi = "10.1083/jcb.200311011",
language = "English",
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 - Polar, Yesim

AU - Sier, Deborah

AU - Anastasiadis, Panos

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 -