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Abstract

Volume 12, Issue 2 (March 2010) 12, 186–195; 10.1038/aja.2009.76

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Zhe-Wei Zhang1, Zhi-Ming Yang2, Yi-Chun Zheng1 and Zhao-Dian Chen3

1 Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
2 Department of Radiation Oncology, Division of Molecular Radiation Science, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA
3 Department of Urology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China

Correspondence: Prof. Zhao-Dian Chen, chenzhaodian@yahoo.com.cn

Received 15 July 2009; Revised 4 August 2009; Accepted 28 October 2009; Published online 25 January 2010.

Abstract

The androgen receptor (AR) and its coregulators have important roles in the carcinogenesis of prostate cancer. p53 is an important tumour suppressor gene, and the absence of a fundamental p53 response may predispose to cancer. Transgelin, known as an ARA54-associated AR inhibitor, can suppress AR function in LNCaP cells. In addition to these effects, we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms, especially the interaction between transgelin and p53. Cell counting, flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin, we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.

Keywords: androgen receptor; apoptosis; mitochondria; p53; prostate cancer; transgelin

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.