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Research Paper
Aberration in the Expression of the Retinoid Receptor, RXRa, in Prostate Cancer
Chen Zhong, Shangxin Yang, Jiapeng Huang, Michael B. Cohen, and Pradip Roy-Burman
volume 2 | issue 2
march/april 2003Pages: 179-184
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There is ample evidence for a role for retinoids in the development and maturation of prostatic epithelium. In recent experiments with conditional disruption of a specific retinoid receptor, namely, RXRa in the prostatic epithelium of the mouse, we observed that a major component of retinoid action in the prostate is indeed mediated by RXRa. The results clearly indicated that the inactivation of RXRa in the prostate epithelium leads to the development of preneoplastic lesions (Huang et al. Cancer Res. 62: 4812-4819, 2002). To determine the relation of this finding to human prostate cancer, we examined the expression of RXRa protein in human prostate cancer cell lines by western blotting and prostate cancer specimens by immunohistochemistry. Relative to the "normal" prostate epithelial cells, there was approximately two- to nine-fold decrease in the full-length 54 kD RXRa protein in each of the seven different prostate cancer cell lines tested. Similarly, while RXRa immunostaining was uniformly strong in the nuclei of most of the benign prostatic epithelial cells of the thirteen adenocarcinoma specimens tested, a highly heterogeneous pattern of expression was detected in the malignant epithelium, with some areas with low or no staining, others with mostly cytoplasmic staining, and some with both nuclear and cytoplasmic immunoreactivity. To evaluate the effect of RXRa modulation on the biologic properties of prostate cancer cell lines, we used a lentivirus expression system to overexpress RXRa in CWR22R prostate cancer cells that basally expressed a marginal level of the receptor. The sorted RXRa-transduced cells were compared to the corresponding vector control cells for proliferative and apoptotic properties. A correlation of reduction of cell growth or increased susceptibility to apoptosis with increases in the level of RXRa nuclear receptor was demonstrated. These effects were further enhanced when the cell culture medium was supplemented with a retinoid receptor panagonist, 9-cis retinoic acid. Together, these data support the notion that, like in mouse prostate, loss or reduction of RXRa activity might be a critical factor in prostate tumorigenesis in humans.
Key Words
Retinoid receptor RXRa, 9-cis retinoic acid, Prostate cancer cells, Lentivirus vectors, Apoptosis
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.