Increased Heparanase Expression Is Caused by Promoter Hypomethylation and Up-Regulation of Transcriptional Factor Early Growth Response-1 in Human Prostate Cancer
作者： Shinji Urakami , Hideki Enokida , Hiroaki Shiina , Mikio Igawa , Leopoldo A. Ribeiro-Filho
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摘要: Purpose: Heparanase degrades heparan sulfate and has been implicated in tumor invasion metastasis. The transcription factor, early growth response 1 (EGR1), is associated with the inducible of heparanase gene. We hypothesize that CpG hypomethylation promoter coupled up-regulation EGR1 levels may induce expression human prostate cancer. Experimental Design: Cultured cancer cell lines (Du145, DuPro, LNCaP, PC-3) without 5′-aza-2-deoxycytidine treatment, 177 samples, 69 benign prostatic hyperplasia (BPH) samples were used. frequency level methylation analyzed by methylation-specific primers which covered core binding motif (GGCG) or SP1 (GGGCGG) both. Results: In cultured Du145, PC-3 lines, mRNA transcripts significantly increased after suggesting was involved regulation transcript. Significantly higher found BPH than ( P Conclusions: To our knowledge this first comprehensive study demonstrating tissues due to factor EGR1.
aacrjournals.org参考文章(39)
A. Aoike, N. Ohtani-Fujita, T. Sakai, Paul D Robbins, T. Fujita, N. E. Osifchin, CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene Oncogene. ,vol. 8, pp. 1063- 1067 ,(1993)
Israel Vlodavsky, Yael Friedmann, Michael Elkin, Helena Aingorn, Ruth Atzmon, Rivka Ishai-Michaeli, Menachem Bitan, Orit Pappo, Tuvia Peretz, Israel Michal, Larissa Spector, Iris Pecker, Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nature Medicine. ,vol. 5, pp. 793- 802 ,(1999) , 10.1038/10518
Mark D. Hulett, Craig Freeman, Brenton J. Hamdorf, Rohan T. Baker, Matthew J. Harris, Christopher R. Parish, Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nature Medicine. ,vol. 5, pp. 803- 809 ,(1999) , 10.1038/10525
Cathy K. Naughton, William J. Catalona, Joseph J.H. Ackerman, Jeffrey I. Gordon, Peter A. Humphrey, Jeffrey Milbrandt, Sarki A. Abdulkadir, Zhican Qu, Emily Garabedian, Sheng-Kwei Song, Thomas J. Peters, John Svaren, Joseph M. Carbone, Impaired prostate tumorigenesis in Egr1-deficient mice. Nature Medicine. ,vol. 7, pp. 101- 107 ,(2001) , 10.1038/83231
Maurizio Zangari, Bart Barlogie, Ralph D. Sanderson, Lija Joseph, Veronica MacLeod, Hua-Quan Miao, Fenghuang Zhan, John Shaughnessy, Thomas Kelly, Yang Yang, Elizabeth Navarro, Paul Kussie, Jonathan Casciano, Yan Huang, High heparanase activity in multiple myeloma is associated with elevated microvessel density. Cancer Research. ,vol. 63, pp. 8749- 8756 ,(2003)
Rajvir Dahiya, Celeste Lee, Joseph McCarville, Weixing Hu, Gurjit Kaur, Guoren Deng, High frequency of genetic instability of microsatellites in human prostatic adenocarcinoma. International Journal of Cancer. ,vol. 72, pp. 762- 767 ,(1997) , 10.1002/(SICI)1097-0215(19970904)72:5<762::AID-IJC10>3.0.CO;2-B
Shuji Mikami, Kenichi Ohashi, Yutaka Usui, Tetsuo Nemoto, Ken-ichi Katsube, Masaki Yanagishita, Motowo Nakajima, Kyouichi Nakamura, Morio Koike, Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas. Japanese Journal of Cancer Research. ,vol. 92, pp. 1062- 1073 ,(2001) , 10.1111/J.1349-7006.2001.TB01061.X
Yongjing Guo, Pouya Pakneshan, Julienne Gladu, Andrew Slack, Moshe Szyf, Shafaat A Rabbani, None, Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion. Journal of Biological Chemistry. ,vol. 277, pp. 41571- 41579 ,(2002) , 10.1074/JBC.M201864200
J. G. Herman, J. R. Graff, S. Myohanen, B. D. Nelkin, S. B. Baylin, Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 9821- 9826 ,(1996) , 10.1073/PNAS.93.18.9821
Israel Vlodavsky, Orit Goldshmidt, Eyal Zcharia, Shula Metzger, Tova Chajek-Shaul, Ruth Atzmon, Zehava Guatta-Rangini, Yael Friedmann, Molecular properties and involvement of heparanase in cancer progression and normal development Biochimie. ,vol. 83, pp. 831- 839 ,(2001) , 10.1016/S0300-9084(01)01318-9