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 growt h was studied using RNAase protection assays of activin receptors, inhibin/ activin subunits and follistatin mRNAs in the human prostatic carcinoma cel l 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 prostat e epithelial cells, with significantly fewer levels of ActRIB mRNA in prost ate tumour material when compared to non-malignant tissue (P < 0.05; Mann-W hitney U-test). Inhibin/activin beta A- and beta B-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expresse d significantly lower amounts of beta B-subunit mRNA when compared to andro gen-dependent xenografts (P < 0.05). While BB-subunit mRNA was expressed by LNCaP-FGC and -LNO cells, virtually no expression was found in the androge n-independent LNCaP-R line. Inhibin alpha-subunit mRNA levels were low or u ndetectable in all samples investigated. Follistatin mRNA was undetectable in LNCaP-sublines, while low levels were found in prostatic tissues. In and rogen-independent LNCaP-R cells, activin inhibited cell growth in a dose-de pendent manner. These results suggest that prostate tumour progression is a ccompanied by a decrease of the inhibitory effect of locally produced activ in 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.