ATBF1研究综述

AT模体结合因子1(ATBF1)是一个新发现的抑癌基因,从人肝癌细胞HuH-7中分离得到。ATBF1可与甲胎蛋白基因增强子中AT富含原件结合,其表达产物是目前发现的分子量最大的转录调节因子。ATBF1基因表达过程中,通过选择性剪接产生ATBF1-A和ATBF1-B两种mRNA,这两种mRNA对AFP表达的调节具有相互对抗作用。ATBF1-A是ATBF1基因的主要表达形式,能抑制癌细胞生长;而ATBF1-B则能促进癌细胞增殖。ATBF1作为抑癌基因,为肿瘤的治疗带来新希望,但目前学术界对ATBF1的研究仍然有限。本文重点对ATBF1在神经系统、乳腺癌、胃癌、肝癌、结直肠癌以及其他肿瘤中的研究作综述,以期进一步明确ATBF1的抑癌机制。     

Susceptibility to killer T cells of gastric cancer cells enhanced by Mitomycin-C involves induction of ATBF1 and activation of p21 (Waf1/Cip1) promoter

Alpha-fetoprotein (AFP) expression is observed in embryonic tissues and, the expression of this protein is absent in normal adult tissues. The re-elevation of serum AFP strongly suggests generation of a malignant tumor in an adult. We demonstrated here that AFP-producing gastric cancer (AFP-gastric cancer) could be treated by a combination therapy with a low dose of Mitomycin-C (MMC) and lymphokineactivated killer T (LAK-T) cells. Treatment with MMC of AFP-gastric cancer cells enhanced their susceptibility to LAK-T cells and induced ATBF1 gene expression. We revealed here a novel signal pathway for regulation of the cell cycle of AFP-gastric cancer cells through ATBF1, which enhances the promoter activity of the p21 (Waf1/Cip1) gene. Immunoprecipitation revealed the direct interaction between ATBF1 and p53. Overexpressed ATBF1 stimulated p21 (Waf1/Cip1) promoter activity up to 4-fold compared with basal activity. The expression level of ATBF1 mRNA was doubled by MMC (0.05 microg/ml) treatment. The MMC treatment and ATBF1 overexpression synergistically activated the p21 (Waf1/Cip1) promoter activity in a dose-dependent manner up to 7-fold compared with basal activity.     

Heterozygous deletion of Atbf1 by the Cre‐loxP system in mice causes preweaning mortality

ATBF1 is a large nuclear protein that contains multiple zinc‐finger motifs and four homeodomains. In mammals, ATBF1 regulates differentiation, and its mutation and/or downregulation is involved in tumorigenesis in several organs. To gain more insight into the physiological functions of ATBF1, we generated and validated a conditional allele of mouse Atbf1 in which exons 7 and 8 were flanked by loxP sites (Atbf1^flox). Germline deletion of a single Atbf1 allele was achieved by breeding to EIIa‐cre transgenic mice, and Atbf1 heterozygous mice displayed reduced body weight, preweaning mortality, increased cell proliferation, and attenuated cytokeratin 18 expression, indicating haploinsufficiency of Atbf1. Floxed Atbf1 mice will help us understand such biological processes as neuronal differentiation and tumorigenesis. genesis 1–9, 2012. © 2012 Wiley Periodicals, Inc.