Colonocyte differentiation is associated with increased expression and altered distribution of protein kinase C isozymes

G. Verstovsek, A. Byrd, M. R. Frey, N. J. Petrelli, J. D. Black

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Background and Aims: Colon cancer cells express reduced levels of protein kinase C (PKC). This study examines the regulation of PKC isozymes in normal colonic epithelium, as a basis for understanding the significance of alterations in this enzyme system in colon carcinogenesis. Methods: The expression and localization of PKC isozymes in mouse and rat colonocytes at different developmental stages were determined using a combined morphological and biochemical approach. PKC α expression was compared in colonic adenocarcinomas and adjacent normal mucosa by immunoblot analysis. Results: Mouse and rat colonocytes express PKC α, βII, δ, ε, and ζ. Relatively low levels of these isozymes were detected in proliferating cells of the crypt base, predominantly in the cytosolic compartment. Coincident with colonocyte growth arrest/differentiation, PKC isozyme expression markedly increased in both the cytosolic and, more significantly, in the membrane/cytoskeletal fraction. Colonic tumors express reduced levels of PKC α, an isozyme that has been implicated in negative control of intestinal cell growth. Conclusions: These findings are supportive of a role for certain PKC isozyme(s) in signaling pathways mediating postmitotic events in colonocytes in situ, and suggest that diminished activity of these pathway(s) may contribute to the alterations in growth control/differentiation associated with colonic neoplasia.

Original languageEnglish (US)
Pages (from-to)75-85
Number of pages11
JournalGastroenterology
Volume115
Issue number1
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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