AIMS: alpha-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. METHODS AND RESULTS: Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum alpha-fetoprotein level. CONCLUSIONS: The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations.
AIMS: alpha-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. METHODS AND RESULTS: Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum alpha-fetoprotein level. CONCLUSIONS: The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations.
Authors: Xue Yang; Jee Hoon Song; Yulan Cheng; Wenjing Wu; Tushar Bhagat; Yiting Yu; John M Abraham; Sariat Ibrahim; William Ravich; Bani Chander Roland; Mouen Khashab; Vikesh K Singh; Eun Ji Shin; Xiao Yang; Amit K Verma; Stephen J Meltzer; Yuriko Mori Journal: Gut Date: 2013-09-02 Impact factor: 23.059
Authors: Kathryn A O'Donnell; Vincent W Keng; Brian York; Erin L Reineke; Daekwan Seo; Danhua Fan; Kevin A T Silverstein; Christina T Schrum; Wei Rose Xie; Loris Mularoni; Sarah J Wheelan; Michael S Torbenson; Bert W O'Malley; David A Largaespada; Jef D Boeke Journal: Proc Natl Acad Sci U S A Date: 2012-05-03 Impact factor: 11.205