This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, B. Articles by Kyprianou, N. Search for Related Content PubMed PubMed Citation Articles by Zhu, B. Articles by Kyprianou, N.

Prohibitin and Cofilin Are Intracellular Effectors of Transforming Growth Factor ß Signaling in Human Prostate Cancer Cells

¹ Division of Urology and ² Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky

Requests for reprints: Natasha Kyprianou, Division of Urology, MS-283, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298. Phone: 859-323-9812; Fax: 859-323-1944; E-mail: natasha{at}uky.edu.

A proteomic analysis was pursued to identify new signaling effectors of transforming growth factor ß1 (TGF-ß1) that serve as potential intracellular effectors of its apoptotic action in human prostate cancer cells. The androgen-sensitive and TGF-ß-responsive human prostate cancer cells, LNCaP TßRII, were used as in vitro model. In response to TGF-ß, significant posttranslational changes in two proteins temporally preceded apoptotic cell death. TGF-ß mediated the nuclear export of prohibitin, a protein involved in androgen-regulated prostate growth, to the cytosol in the LNCaP TßRII cells. Cofilin, a protein involved in actin depolymerization, cell motility, and apoptosis, was found to undergo mitochondrial translocation in response to TGF-ß before cytochrome c release. Loss-of-function approaches (small interfering RNA) to silence prohibitin expression revealed a modest decrease in the apoptotic response to TGF-ß and a significant suppression in TGF-ß-induced cell migration. Silencing Smad4 showed that the cellular localization changes associated with prohibitin and cofilin action in response to TGF-ß are independent of Smad4 intracellular signaling. (Cancer Res 2006; 66(17): 8640-7)

This article has been cited by other articles:

				C. Rojas-Cartagena, P. Ortiz-Pineda, F. Ramirez-Gomez, E. C. Suarez-Castillo, V. Matos-Cruz, C. Rodriguez, H. Ortiz-Zuazaga, and J. E. Garcia-Arraras Distinct profiles of expressed sequence tags during intestinal regeneration in the sea cucumber Holothuria glaberrima Physiol Genomics, October 19, 2007; 31(2): 203 - 215. [Abstract] [Full Text] [PDF]