Increased expression of heparin binding EGF (HB-EGF), amphiregulin, TGFα and epiregulin in androgen-independent prostate cancer cell lines

Background. The proliferation of androgen-independent prostate cancer cell lines has previously been shown to be influenced by an autocrine loop of the epidermal growth factor (EGF) system. This observation has alerted us to study the expression of ligands and receptors from the ECF-system in prostate cell lines. Methods. The expression of the EGF system was determined by quantitative RT-PCR and ELISA in the normal prostate epithelial cell line (PNT1A), in the androgen sensitive- (LNCaP), and the androgen-independent (DU145 and PC3) prostate cancer cell lines. Results. The expression of mRNA for the ligands TGF alpha, amphiregulin, HB-EGF and epiregulin were increased 10 to 100 fold in androgen-independent cells, as compared to LNCaP and PNT1A cells. Expression of mRNA for the ligands EGF and betacellulin and of the receptors HER1 and HER2 were similar in all lines investigated except LNCaP cells which exhibit low expression of HER1. Similar results were obtained by ELISA. Conclusions. The data indicates a selective up-regulation of a subclass of ligands of the EGF-system in androgen-independent prostate cancer cell lines. We suggest this could be a mechanism to escape androgen dependence in prostate cancer.