Differential Expression of Transcriptional Variants of XAF1 in Colorectal Neoplasms / 胃肠病学

ABSTRACT

Background:The tumor suppressor,X-linked inhibitor of apoptosis(XIAP)-associated factor 1(XAF1)is a XIAP-binding protein that antagonizes the anti-caspase activity of XIAP,thereby enhancing apoptosis. Transcriptional variants of XAF1 have been detected in various tumor cells,however,the expression profile of these transcriptional variants in colorectal neoplasms remains unclear. Aims:To investigate the expressions of XAF1 and its transcriptional variants in different colorectal tissues and their roles in tumorigenesis and development of colorectal neoplasms. Methods:Samples of colorectal cancer and paired adjacent tissue,hyperplastic polyp,adenomatous polyp,and normal colorectal mucosa were collected from surgical operation or endoscopic biopsies. XAF1 protein expression was detected by immunohistochemistry and Western blotting,and the transcriptional variants of XAF1 were detected by RT-PCR. Results:Compared with normal colorectal mucosa,the expression level of XAF1 protein in nucleus was significantly reduced( P 0. 05)in hyperplastic polyp,adenomatous polyp,and cancerous tissue,and the overall expression level of XAF1 protein was decreased(P <0. 05). XAF1A protein expression in cancerous tissue was significantly reduced when compared with the paired adjacent tissue(P < 0. 05). mRNA expressions of three transcriptional variants of XAF1,XAF1A,XAF1B and XAF1C were all significantly lower in neoplastic tissues than in normal mucosa(P < 0. 05). Conclusions:XAF1 and its transcriptional variants are differentially expressed in colorectal neoplasms and normal colorectal mucosa. These changes occurred initially in adenomatous polyp accompanied by a redistribution of XAF1 from nucleus to cytoplasm. Post-transcriptional modification may affect XAF1 gene function.