Alternations of Transcriptional Regulation in Oral Cancers and Analysis of Tumor Suppressive functions of p300 Transcriptional Co-activator

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The p300 acetyltransferase/transcriptional coactivator plays key roles in the regulation of cell proliferation and differentiation. Although p300 is targeted for mutations in human carcinomas, a role for p300ICBP in tumorigenesis is still remains poorly understood. In this study, we have identified p300 in two lines of human carcinoma cells (Ohshima et al. 2001, Suganuma et al. 2003). We have demonstrated that reintroduction of wild-type p300 suppressed growth of human carcinoma cells lacking normal p300, and that p300 plays an important role in the TGFJ3 signaling pathway, which is important for the negative regulation of epithelial cell growth (Suganuma et al. 2003).To further elucidate mechanisms of tumorigenesis of oral carcinomas, we have investigated regulation of the RB tumor suppressor protein and the interaction between chromatin DNA and nuclear matrix. We have obtained several observations. (1) Cytoplasinic sequestration of cyclin D1, which is critical for RB phosphorylation, plays an important role for cell cycle exit and survival of terminally differentiated cardiomyocytes and neurons, respectively (Tamamori-Adachi et al. 2003ÅASumrejkanchanakij et al. 2003). (2) The nuclear-matrix-binding protein E2FBP1/DRIL1 is regulated by the p53 tumor suppressor (Ma et al. 2003). (3) Distinct recruitment of transcription regulatory complexes to chromatin DNA mediates activation and repression of an E2F target gene, which is regulated by the RB family proteins (Araki et al. 2003).