role of heparan sulfate 2-o-sulfotransferase in prostate cancer cell proliferation, invasion, and growth factor signaling硫酸乙酰肝素的作用2-o-sulfotransferase在前列腺癌的细胞增殖,入侵和生长因子信号.pdfVIP

Hindawi Publishing Corporation Prostate Cancer Volume 2011, Article ID 893208, 14 pages doi:10.1155/2011/893208 Research Article Role of Heparan Sulfate 2-O-Sulfotransferase in Prostate Cancer Cell Proliferation, Invasion, and Growth Factor Signaling Brent W. Ferguson and Sumana Datta Department of Biochemistry/Biophysics, Texas AM University, MS 2128, College Station, TX 77845, USA Correspondence should be addressed to Brent W. Ferguson, brentwade@ Received 13 April 2011; Revised 11 July 2011; Accepted 17 August 2011 Academic Editor: Shuyuan Yeh Copyright © 2011 B. W. Ferguson and S. Datta. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor signaling in prostate cancer progression. The degree of sulfate modification on the covalently attached heparan sulfate (HS) chains is one of the determining factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS chains via a series of O-sulfotransferases. In the present study, we demonstrate that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We also show that a decrease in invasion due to 2OST siRNA is associated with an increase in actin and E-cadherin accumulation at the cell surface. 2OST expression correlates with increasing metastatic potential in this model. We demonstrate that 2OST expression is upregulated by the stress-inducible transcription factors HIF1α, ATF2, and NFκB. Chromatin immunoprecipitation analysis suggests that HIF1α and ATF2 act directly on the 2OST