tailieunhanh - Báo cáo khoa học: Wild-type p53 enhances annexin IV gene expression in ovarian clear cell adenocarcinoma

The protein annexin IV (ANX4) is elevated specifically and characteristi-cally in ovarian clear cell adenocarcinoma (CCA), a highly malignant histo-logical subtype of epithelial ovarian cancer. On the basis of the hypothesis that the expression of ANX4in CCA is regulated by a unique transcription mechanism, we explored thecis-elements involved in CCA-specific ANX4 expression using a luciferase reporter. | ijFEBS Journal Wild-type p53 enhances annexin IV gene expression in ovarian clear cell adenocarcinoma xz I KU I l-XM I A I 1 I I I I 1 I HU 2 II I 2 I Yusuke Masuishi Noriaki Arakawa Hiroshi Kawasaki Etsuko Miyagi Fumiki Hirahara and Hisashi Hirano1 1 Department of Supramolecular Biology Graduate Schoolof Nanobioscience Yokohama City University Japan 2 Department of Obstetrics and Gynecology Yokohama City University Schoolof Medicine Japan Keywords annexin IV clear cell adenocarcinoma ovarian cancer p53 promoter Correspondence N. Arakawa or H. Hirano Department of Supramolecular Biology Graduate School of Nanobioscience Yokohama City University 1-7-29 Suehiro-cho Tsurumi-ku Yokohama 230-0045 Japan Fax 81 45 508 7667 Tel 81 45 508 7247 E-mail arakawa@ These authors contributed equally to this work Received 13 December 2010 revised 25 January 2011 accepted 21 February 2011 doi The protein annexin IV ANX4 is elevated specifically and characteristically in ovarian clear cell adenocarcinoma CCA a highly malignant histological subtype of epithelial ovarian cancer. On the basis of the hypothesis that the expression of ANX4 in CCA is regulated by a unique transcription mechanism we explored the cis-elements involved in CCA-specific ANX4 expression using a luciferase reporter. We compared the transcriptional activities of the region from -1534 to 1010 relative to the ANX4 transcription start site in CCA and non-CCA-type cell lines and found that two repeated binding motifs for the tumor suppressor protein p53 in the first intron of ANX4 were involved in CCA-specific transcriptional activity. Furthermore chromatin immunoprecipitation showed that endogenous p53 bound to this site in CCA cell lines. Moreover the use of short interference RNA to silence the p53 gene decreased the transcriptional activity and mRNA expression of ANX4 in CCA cell lines. Thus the ANX4 gene is at least in part regulated by p53 in CCA cells. .