Variations in activin receptor, inhibin/activin subunit and follistatin mRNAs in human prostate tumour tissues

The possible role of activin in the regulation of malignant prostatic growth was studied using RNAase protection assays of activin receptors, inhibin/activin subunits and follistatin mRNAs in the human prostatic carcinoma cell lines LNCaP-FGC, -R and -LNO, in human prostatic carcinoma xenografts and in human prostatic tissue. Activin receptor types IA (ActRIA), IB (ActRIB), IIA (ActRIIA) and [IB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly fewer levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test). Inhibin/activin beta A- and beta B-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of beta B-subunit mRNA when compared to androgen-dependent xenografts (P < 0.05). While BB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androgen-independent LNCaP-R line. Inhibin alpha-subunit mRNA levels were low or undetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In androgen-independent LNCaP-R cells, activin inhibited cell growth in a dose-dependent manner. These results suggest that prostate tumour progression is accompanied by a decrease of the inhibitory effect of locally produced activin by either a decrease in the expression of activin beta B-subunit mRNA or by a decrease of ActRIB mRNA levels. (C) 2000 Cancer Research Campaign.