EXPRESSION OF MESSENGER-RNA FOR EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA AND THEIR RECEPTOR IN HUMAN PROSTATE TISSUE AND CELL-LINES

Enhanced expression of the epidermal growth factor receptor (EGFR) or its ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) can increase signalling via receptor-mediated pathways which may lead to excessive proliferation and cellular transformation. Such autocrine regulation of growth has been demonstrated for prostate cancer cell lines in culture but its role in prostate cancer in vivo has not been established. To assess the potential of such a mechanism, we have examined the pathway components in prostate carcinomas (CaP) in comparison with non-malignant benign prostatic hyperplasias (BPH). In the present study, we investigate the dosage, structure and expression of EGF, TGF-alpha and EGFR genes in a series of 34 human prostate samples and 3 prostate cancer cell lines. All of the samples contained transcripts from each of the genes. The expression of pre-pro-TGF-a mRNA and pre-pro-EGF mRNA were significantly higher in CaP (n = 13) than BPH (n = 21) specimens (p < 0.05). The androgen-respon sive prostatic carcinoma cell line, LNCaP, expressed high levels of EGF mRNA while the androgen-independent DU145 and PC-3 cell, lines expressed high levels of TGF-alpha mRNA and EGFR mRNA. In general, overexpression of these mRNAs was not associated with amplification or detectable gene rearrangment; only DU145 cells demonstrated any alteration in these genes, with apparent amplification of the TGF-alpha gene. Relative to BPH, all prostate carcinomas and cell lines studied had elevated levels of mRNA for one or both mRNA coding for the ligands for EGFR. Thus enhanced expression of the ligands and co-expression of the EGF receptor are frequent events in human prostate tumors, consistent with the cell culture data supporting autocrine growth regulation via EGFR-mediated pathways.