Regulation of rat DOC-2 gene during castration-induced rat ventral prostate degeneration and its growth inhibitory function in human prostatic carcinoma cells.

Authors: Tseng, CP  Ely, BD  Li, Y  Pong, RC  Hsieh, JT 
Citation: Tseng CP, etal., Endocrinology 1998 Aug;139(8):3542-53.
Pubmed: (View Article at PubMed) PMID:9681506
DOI: Full-text: DOI:10.1210/endo.139.8.6159

Androgen is a mitogen as well as a morphogen for prostatic epithelium. However, the detailed mechanisms of these distinct androgenic actions have not yet been delineated. Therefore, we employed differential display PCR to unveil any potential genes that may be involved in these processes. In this study, we report the isolation and characterization of two alternative splicing forms (p82 and p59) of C9 complementary DNA, the rat homolog of the human deletion of ovarian carcinoma 2 (DOC-2) gene and mouse p96 phosphoprotein, from rat ventral prostate (VP). We found that C9 was up-regulated in rat VP after castration, suggesting that C9 may be regulated by androgen receptor directly or indirectly during prostate degeneration. A similar regulatory pattern was also observed in both the seminal vesicle and dorsolateral prostate, but not in the coagulating gland or other androgen-independent organs. Immunohistochemical analysis of rat VP demonstrated that C9 is detected in the basal epithelia and surrounding stromal cells after prolonged castration. Ribonuclease protection assay and Western blot analysis revealed that p59 is the predominant C9 isoform in rat VP. To unveil the function of C9 in cell growth, we transfected p59 complementary DNA into the C4-2 cells, a derivative of the LNCaP prostatic carcinoma cell line. The p59 stable transfectants exhibited a slower growth rate and an increase in the cell fraction in the G1 phase under our experimental conditions. These data indicate that C9-p59 has growth inhibitory activity for prostatic epithelial cells. Taken together, our results suggest that C9 is up-regulated during prostate degeneration process and may play an active role in the proliferation and differentiation of prostatic epithelium.

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CRRD ID: 728288
Created: 2003-11-13
Species: All species
Last Modified: 2003-11-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.