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Effects of IFN‐β and 1,25‐dihydroxyvitamin D3 on cellular proliferation, induction of 2′,5′‐oligoadenylate (2‐5A) synthetase and changes in immunoreactive pRB/p53 in human prostatic JCA‐1 cells
Author(s) -
Faiella Louis,
Ng Chunyung,
Hsieh Tzechen,
Wu Joseph M.,
Mallouh Camille
Publication year - 1996
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549600201252
Subject(s) - endocrinology , medicine , chemistry , biology , microbiology and biotechnology
The combined antimitogenic effects of IFN‐β and 1,25‐dihydroxyvitamin D3 (vit. D3) were investigated by treating the androgen‐independent JCA‐1 cells, established from the primary prostatic tumor site prior to anti‐hormonal therapy, with IFN‐β (1000 IU/ml), vit. D3 (100 nM), and both agents. Cell growth, changes in overall RNA and protein contents, and cell cycle regulatory proteins pRB/p53 were determined. After a 24 h exposure, a significant reduction in cell proliferation was observed in all three conditions. IFN‐β, vit D3, and their combination elicited, respectively, a 1.7‐, 1.6‐ and 2.5‐fold increase in total RNA and a corresponding 1.4‐, 1.2‐ and 1.7‐fold increase in soluble proteins. The IFN‐inducible 2‐5A synthetase activity was elevated by 15‐, 1.4‐ and 21‐fold, respectively. No differences in cell cycle phase distribution were found between control and treated samples. However, a significant change in pRB and p53 expression was observed upon exposure to these agents. A progressive increase in total pRB was observed in untreated JCA‐1 cells, with the 48 h culture showing a 1.9‐fold increase over the 6 h culture. The ratio of phosphorylated to the nonphosphorylated forms of pRB, however, decreased from 3.00 at 6 h to 1.2 at 48 h. The overall pRB increase as well as the modified:unmodified protein ratio change were both markedly decreased when the cells were treated with IFN‐β, vit. D3, or their combination. With p53, a similar progressive increase was also observed in control cells, which was largely abolished by IFN‐β but only partially blocked by vit. D3. The combination of IFN‐β and vit. D3 gave results similar to samples receiving vit. D3 alone suggesting that the effects of IFN‐β, insofar as p53 modulation is concerned, is distal to the effects of vit. D3.