Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo.

Abstract

Gene alterations in tumor cells that confer the ability to grow under nutrient- and mitogen-deficient conditions constitute a competitive advantage that leads to more-aggressive forms of cancer. The atypical protein kinase C (PKC) isoform, PKCzeta, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKCzeta-deficient mice display increased Ras-induced lung carcinogenesis, suggesting a new role for this kinase as a tumor suppressor in vivo. We also show that Ras-transformed PKCzeta-deficient lungs and embryo fibroblasts produced more interleukin-6 (IL-6), which we demonstrate here plays an essential role in the ability of Ras-transformed cells to grow under nutrient-deprived conditions in vitro and in a mouse xenograft system in vivo. We also show that PKCzeta represses histone acetylation at the C/EBPbeta element in the IL-6 promoter. Therefore, PKCzeta, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis.

• Authors: Anita S Galvez, Angeles Duran, Juan F Linares, Peterson Pathrose, Elias A Castilla, Shadi Abu-Baker, Michael Leitges, Maria T Diaz-Meco, Jorge Moscat
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 29 Issue 1 Pg. 104-15 (Jan 2009) ISSN: 1098-5549 [Electronic] United States
• PMID: 18955501 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• NF-kappa B
• protein kinase C zeta
• Protein Kinase C

Topics

• Animals
• Cell Line
• Cell Proliferation
• Cell Transformation, Neoplastic (pathology)
• Gene Expression Regulation, Neoplastic
• Genes, ras
• Humans
• Interleukin-6 (genetics)
• Lung Neoplasms (enzymology, genetics, metabolism, pathology)
• Mice
• NF-kappa B (metabolism)
• Promoter Regions, Genetic (genetics)
• Protein Kinase C (deficiency, metabolism)
• Serum
• Transcription, Genetic