The Polycomb group (PcG) gene products form multimeric protein complexes and contribute to anteriorposterior (A-P) specification via the transcriptional regulation of Hox cluster genes. The Drosophila polyhomeotic genes and their mammalian orthologues, Phc1, Phc2, and Phc3, encode nuclear proteins that are constituents of evolutionarily conserved protein complexes designated class II PcG complexes. In this study, we describe the generation and phenotypes of Phc2-deficient mice. We show posterior transformations of the axial skeleton and premature senescence of mouse embryonic fibroblasts associated with derepression of Hox cluster genes and Cdkn2a genes, respectively. Synergistic actions of a Phc2 mutation with Phc1 and Rnf110 mutations during A-P specification, coimmunoprecipitation of their products from embryonic extracts, and chromatin immunoprecipitation by anti-Phc2 monoclonal antibodies suggest that Hox repression by Phc2 is mediated through the class II PcG complexes, probably via direct binding to the Hox locus. The genetic interactions further reveal the functional overlap between Phc2 and Phc1 and a strict dose-dependent requirement during A-P specification and embryonic survival. Functional redundancy between Phc2 and Phc1 leads us to hypothesize that the overall level of polyhomeotic orthologues in nuclei is a parameter that is critical in enabling the class II PcG complexes to exert their molecular functions.

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KAI1 is a tumor suppressor gene originally identified in prostate cancer. Recent studies of oral cancer, including our investigations, have shown frequent down-regulation of KAI1 expression in many tumor types, whereas mutation of the gene is infrequent. However, the role of the down-expression of KAI1 in oncogenesis and the progression of oral carcinoma remains unclear. In this study, we analyzed the mutational status of KAI1 and both the mRNA and protein levels of the gene in a series of gingival carcinomas and precancerous lesions (20 leukoplakias, 50 squamous cell carcinomas, and 20 lymph node metastatic tumors) . Although no mutation was found in any sample tested, immunohistochemical studies revealed high frequencies of KAI1 down-regulation not only in the metastatic tumors (20 of 20, 100 %) , but also in the primary carcinomas (39 of 50, 78 %) and leukoplakias (9 of 20, 45 %). Down-regulation of KAI1 protein expression was significantly related to carcinogenesis and metastasis (precancerous lesions, primary carcinomas, and metastatic tumors) (p<0.001) as well as to lymph node metastasis (p=0.0022). RT PCR analysis confirmed these results. Therefore, suppressed expression of KAI1 was suggested to play clinically significant roles in carcinogenesis and lymph node metastasis .

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