Title | Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Galvez AS, Duran A, Linares JF, Pathrose P, Castilla EA, Abu-Baker S, Leitges M, Diaz-Meco MT, Moscat J |
Journal | Mol Cell Biol |
Volume | 29 |
Issue | 1 |
Pagination | 104-15 |
Date Published | 2009 Jan |
ISSN | 1098-5549 |
Keywords | Animals, Cell Line, Cell Proliferation, Cell Transformation, Neoplastic, Gene Expression Regulation, Neoplastic, Genes, ras, Humans, Interleukin-6, Lung Neoplasms, Mice, NF-kappa B, Promoter Regions, Genetic, Protein Kinase C, Serum, Transcription, Genetic |
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. |
DOI | 10.1128/MCB.01294-08 |
Alternate Journal | Mol Cell Biol |
PubMed ID | 18955501 |
PubMed Central ID | PMC2612492 |
Grant List | R01 AI072581 / AI / NIAID NIH HHS / United States R01-AI072581 / AI / NIAID NIH HHS / United States |
Related Faculty:
Jorge Moscat, Ph.D. Juan Francisco Linares Rodriguez, Ph.D. Maria Diaz-Meco Conde, Ph.D.