1. Effects of bicalutamide and 4OH-tamoxifen on androgen-regulated gene expression in the LNCaP cell line
- Author
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Mangerini R, Argellati F, Ulrich Pfeffer, and Boccardo F
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Male ,Neoplasms, Hormone-Dependent ,Prostatic Neoplasms ,Cell Growth Processes ,Prostate-Specific Antigen ,Gene Expression Regulation, Neoplastic ,Tosyl Compounds ,Tamoxifen ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Nitriles ,Androgens ,Humans ,Anilides ,Kallikreins - Abstract
Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator.We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone.Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression.The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.