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 IIB (ActRIIB) mRNAs were generally expressed in prostate epithelial cells, with significantly lower levels of ActRIB mRNA in prostate tumour material when compared to non-malignant tissue (P < 0.05; Mann-Whitney U-test). Inhibin/activin betaA- and betaB-subunit mRNA expression was also found in prostate tissue. Androgen-independent xenografts expressed significantly lower amounts of betaB-subunit mRNA when compared to androgen-dependent xenografts (P< 0.05). While betaB-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 betaB-subunit mRNA or by a decrease of ActRIB mRNA levels.
van Schaik
R H
RH
Department of Endocrinology & Reproduction, Erasmus University Rotterdam, The Netherlands.
Wierikx
C D
CD
Timmerman
M A
MA
Oomen
M H
MH
van Weerden
W M
WM
van der Kwast
T H
TH
van Steenbrugge
G J
GJ
de Jong
F H
FH
D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; D038681:Follistatin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007265:Inhibins; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D038681:Follistatin; D006023:Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides; D029584:Prostatic Secretory Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C043076:beta-microseminoprotein; C094377:inhibin-alpha subunit; D007265:Inhibins; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II