Erythropoietin And Erythropoietin Receptor In Human Prostate Carcinoma And Androgen-independent Transition Of LNCaP Cell Line Under Hypoxia Environment

Objective To confirm the hypothesis that hypoxia makes an important role in androgern-independent transition of PCa and the corresponding molecularbiological mechanism was further studied. Methods The differential expression of EPO and EPOR among PCa, benign prostate hyperplasia (BPH), high-grade prostate intraepithelial neoplasia (HGPIN) and normal prostate tissue was analyzed by immunohistochemistry assay. Androgen-independent LNCaP cell model was developed under hypoxia; the fluctuation of EPO, EPOR and AR in the level of mRNA and protein was assayed using RT-PCR and western blotting when LNCaP cells were cultured with RPMI1640 and 10% fetal bovine serum (FBS) followed by androgen deprivation under hypoxia. Results Cocurrent up-regulation of EPO and EPOR was only shown in PCa and HGPIN. The hypoxia induced androgen-independent growth of LNCaP cells were successfully observed.; decreased AR but increased EPO/EPOR, no matter mRNA or protein, were shown when LNCaP cells were cultured in 10% FBS RPMI 1640 medium under chronic hypoxia; increased AR mRNA with stable AR protein and more enhanced EPO/EPOR protein expression but decreased EPO/EPOR mRNA were shown when the following androgen deprivation was administrated. Conclusions Up-regulated EPOR may be an early event for prostate carcinogesis and cocurrent up-regulation of EPO and EPOR in PCa suggests the important role of hypoxia in the initiation and development of PCa and EPO-EPOR autocrine loop in androgen-independent transition induced by hypoxia.