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

在1995年克隆了AT基序结合因子1（ATBF 1）cDNA后，我们的目的是阐明肌肉的个体发生和分化以及消化器官中的转录致癌机制。由于ATBF 1是作为甲胎蛋白（AFP）的转录控制因子分离的，我们检测了ATBF 1在几种AFP产生的胃癌中的表达水平。使用八种胃癌细胞株和一些临床病理，我们证明ATBF 1的缺失是胃癌中AFP基因表达的原因（Oncogene 2001，20：869-73）。我们还发现ATBF 1的缺失是产生AFP的胃癌的一个显著特征，可能对其高度恶性性质很重要。接下来，我们使用中胚层分化的模型C2 C12细胞研究了肌细胞分化。在体外，ATBF 1在增殖的C2 C12成肌细胞中表达，但在低血清培养基中诱导成肌分化后，其表达水平降低。C2 C12细胞中ATBF 1的强制表达导致MyoD和肌细胞生成素表达受到抑制，Id 3和细胞周期蛋白D1表达增加，从而抑制低血清中的肌细胞分化。我们认为ATBF 1在维持未分化成肌细胞状态中起作用，其下调是启动C2 C12细胞终末分化的先决条件。(J. 2001，276：25057-25065）。阐明了AFP产生胃癌的致癌转录机制和肌细胞分化的转录调控机制。

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.