Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo |
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Authors: | Galvez Anita S Duran Angeles Linares Juan F Pathrose Peterson Castilla Elias A Abu-Baker Shadi Leitges Michael Diaz-Meco Maria T Moscat Jorge |
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Institution: | Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, 3125 Eden Ave., Cincinnati, OH 45267, USA. |
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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, PKCζ, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKCζ-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 PKCζ-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 PKCζ represses histone acetylation at the C/EBPβ element in the IL-6 promoter. Therefore, PKCζ, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis. |
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