The role of transcription factor ATBF1 for the expression of gastro intestinal phenotype in mucosal cells and gastro inestinal Cancer cells.

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After the cloning of AT Motif Binding Factor 1 (ATBF1) cDNA in 1995 we aimed to elucidate the ontogenesis and differentiation of a muscle and transcriptional carcinogenic mechanism in a digestive organ. Because ATBF1 was isolated as a transcriptional control factor of Alpha-fetoprotein (AFP), we examined the expression level of ATBF1 in several AFP producing gastric cancer. Using eight kinds of gastric cancer cell stocks and some clinical pathology, we demonstrated that the absence of ATBF1 is responsible for AFP gene expression in gastric cancer (Oncogene 2001, 20:869-73). We also revealed that the absence of ATBF1 is a distinct characteristic of AFP producing gastric cancer and might be important for its highly malignant nature. Next we studied about muscle cell differentiation with using the C2C12 cell which was a model of mesoderm differentiation. In vitro, ATBF1 was expressed in proliferating C2C12 myoblasts, but its expression levels decreased upon induction of myogenic differentiation in low serum medium. Forced expression of ATBF1 in C2C12 cells resulted in repression of MyoD and myogenin expression and elevation of Id3 and cyclin D1 expression, leading to inhibition of myogenic differentiation in low serum. We suggested that ATBF1 plays a role in the maintenance of the undifferentiated myoblast state, and its down regulation is a prerequisite to initiate terminal differentiation of C2C12 cells. (J. Biol. Chem. 2001, 276:25057-25065). So we elucidated the carcinogenic transcriptional mechanism of AFP producing gastric cancer and transcriptional regulation mechanism of muscle cell differentiation.