Protein kinase C βII and PKCι/λ

Collaborating partners in colon cancer promotion and progression

Nicole R Murray, Justin Weems, Ursula Braun, Michael Leitges, Alan P Fields

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

We previously showed that elevated expression of either protein kinase CβII (PKCβII) or PKCι/λ enhances colon carcinogenesis in mice. Here, we use novel bitransgenic mice to determine the relative importance of PKCβII and PKCι/λ in colon carcinogenesis in two complimentary models of colon cancer in vivo. Bitransgenic mice overexpressing PKCβII and constitutively active PKCι (PKCβII/caPKCι) or kinase-deficient, dominant-negative PKCι (PKCβII/kdPKCι) in the colon exhibit a similar increase in colon tumor incidence, tumor size, and tumor burden in response to azoxymethane (AOM) when compared with nontransgenic littermates. However, PKCβII/kdPKCι mice develop predominantly benign colonic adenomas, whereas PKCβII/caPKCι mice develop malignant carcinomas. In contrast, PKCβ-deficient (PKCβ-/-) mice fail to develop tumors even in the presence of caPKCι. Our previous data indicated that PKCβII drives tumorigenesis and proliferation by activating β-catenin/Apc signaling. Consistent with this conclusion, genetic deletion of PKCβ has no effect on spontaneous tumorigenesis in Apcmin/+ mice. In contrast, tissue-specific knockout of PKCλ significantly suppresses intestinal tumor formation in Apcmin/+ mice. Our data show that PKCβII and PKCι/λ serve distinct, nonoverlapping functions in colon carcinogenesis. PKCβII is required for AOM-induced tumorigenesis but is dispensable for tumor formation in ApcMin/+ mice. PKCι/λ promotes tumor progression in both AOM- and Apc min/+-induced tumorigenesis. Thus, PKCβII and PKCι, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively.

Original languageEnglish (US)
Pages (from-to)656-662
Number of pages7
JournalCancer Research
Volume69
Issue number2
DOIs
StatePublished - Jan 15 2009

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Colonic Neoplasms
Protein Kinases
Protein Kinase C
Colon
Carcinogenesis
Azoxymethane
Neoplasms
Catenins
Tumor Burden
Adenoma
Rodentia
Phosphotransferases
Carcinoma
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Protein kinase C βII and PKCι/λ : Collaborating partners in colon cancer promotion and progression. / Murray, Nicole R; Weems, Justin; Braun, Ursula; Leitges, Michael; Fields, Alan P.

In: Cancer Research, Vol. 69, No. 2, 15.01.2009, p. 656-662.

Research output: Contribution to journalArticle

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