Protein Kinase C Represses the Interleukin-6 Promoter and Impairs Tumorigenesis In Vivo

• Published in: Molecular and cellular biology 2009-01, Vol.29 (1), p.104-115
• Main 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
• Format: Article
• Language: English
• ISSN: 0270-7306; 1098-5549
• DOI: 10.1128/MCB.01294-08

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, PKC, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKC-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 PKC-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 PKC represses histone acetylation at the C/EBP? element in the IL-6 promoter. Therefore, PKC, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis.