Androgen receptor versus erbB-1 and erbB-2 expression in human prostate neoplasms

Abstract

A subject of current interest, especially in the development of androgen refractory prostate cancer, is the androgen receptor (AR) activation by growth factor receptors. Here, we report our work on the measurement of AR mRNA and protein expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCA) and evaluation of the relationship between AR, erbB-1 and erbB-2 gene expression determined in the same tissue. In order to define AR, erbB-1 and erbB-2 in human prostate neoplasms 36 benign prostatic hyperplasia, 46 prostatic carcinoma and 12 normal prostate gland samples were analysed. According to distant metastasis PCA tissues were divided into two categories: i) T1-4N0-3M0 (25 samples) and ii) T4N2-3M1 (21 samples). AR, erbB-1 and erbB-2 mRNA expression was estimated by RT-PCR. AR protein expression, both in nuclear and cytoplasmic fractions, was measured by Western blot technique. The association of AR mRNA and protein expression with erbB-1 and erbB-2 gene expression was evaluated. It was found that in clinically invasive (group II of PCA) prostate cancer cases AR mRNA expression was significantly correlated with erbB-2 mRNA expression (Spearman R coefficient 0.86, p<0.05). Interestingly, AR protein expression in this group of PCA was determined mainly in nuclear fraction. By Western blot AR protein was identified in 76.0% (16/21) and 23.8% (5/21) of PCA group II nuclear and cytoplasmic fractions, respectively. Furthermore, the mean AR protein level in nuclear fraction of clinically invasive (group II) PCA (0.82+/-0.04) was significantly higher (p<0.05) as compared to the normal group (0.56+/-0.11). In the case of T4N2-3M1 samples, significant correlation between AR protein level in nuclear fraction and erbB-2 mRNA expression (Spearman R coefficient 0.53, p<0.05) was stated.