Reference SummaryMurray NR, J Cell Biol 2004 Mar 15;164(6):797-802

Title

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

Authors

Murray NR; Jamieson L; Yu W; Zhang J; Gokmen-Polar Y; Sier D; Anastasiadis P; Gatalica Z; Thompson EA; Fields AP

Journal

J Cell Biol

Volume

164

Issue

6

Year

2004

Pages

797-802

Abstract

Protein kinase C iota (PKCiota) has been implicated in Ras signaling, however, a role for PKCiota in oncogenic Ras-mediated transformation has not been established. Here, we show that PKCiota is a critical downstream effector of oncogenic Ras in the colonic epithelium. Transgenic mice expressing constitutively active PKCiota in the colon are highly susceptible to carcinogen-induced colon carcinogenesis, whereas mice expressing kinase-deficient PKCiota (kdPKCiota) are resistant to both carcinogen- and oncogenic Ras-mediated carcinogenesis. Expression of kdPKCiota 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 kdPKCiota. Our data demonstrate that PKCiota is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCiota, and Rac1.

Links

J:89285 – Mouse Genome Informatics
15024028 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6 Intestine - Large Intestine - Colon adenoma - tubular
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds? Intestine - Large Intestine - Colon carcinoma in situ
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

63.64

C57BL/6 Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed

C57BL/6-Tg(Fabp2-PRKCI*K274W)#Flds Intestine - Large Intestine - Colon foci - aberrant crypt (ACF)
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed

[not specified]-Krastm3Tyj/+ Tg(Fabp2-PRKCI*K274W)#Flds Intestine - Large Intestine - Colon foci - aberrant crypt (ACF) Intestine - Large Intestine - Colon

observed

[not specified]-Krastm3Tyj/+ Intestine - Large Intestine - Colon foci - aberrant crypt (ACF) Intestine - Large Intestine - Colon

observed

C57BL/6 Intestine - Large Intestine - Colon tumor
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

observed - 20

C57BL/6 Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

C57BL/6-Tg(Fabp2-PRKCI*K274W)#Flds Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

0

C57BL/6-Tg(Fabp2-PRKCI*A120E)#Flds? Intestine - Large Intestine - Colon tumor
  • azoxymethane (AOM)
Intestine - Large Intestine - Colon

63.64