Inhibin subunit gene expression in ovarian cancer

Objective(s), Granulosa cell tumors (GCT) and mucinous cystadenocarcinoma of the ovary are associated with elevated circulating levels of immunoreactive inhibin. Measurement of serum inhibin levels provides a useful tumor marker in the management of ovarian tumors. Inhibin is a dimeric ovarian glycoprotein hormone consisting of one alpha and one of two beta subunits. The beta subunits can dimerize to form activin, Activin is bound and its action modulated by another gonadal peptide, follistatin, In this study the patterns of expression of the three inhibin subunit genes, the follistatin gene, and the activin receptor type II gene have been determined, Methods. Gene expression was analyzed in RNA prepared from 16 primary ovarian tumors using reverse transcriptase-polymerase chain reaction (RT-PCR). Gene-specific primes were used for RT-PCR; the products were analyzed by Southern blot analysis with gene-specific P-32-labeled probes. Results. Widespread expression of these genes was found in all of the tumor types examined. Abundant expression of the inhibin a! subunit gene was observed in the GCT and to a lesser extent in the mucinous and serous tumors, beta subunit expression was also present in the GCT and to a lesser extent in the other tumors. Widespread expression of both the activin receptor type II and the follistatin genes was also observed. Conclusions. Expression of the inhibin subunit genes in GCT and some epithelial tumors confirms that these tumors are the source of the increased immunoreactive inhibin seen in the circulation of patients with ovarian tumors. Expression of the activin receptor type II and follistatin genes suggests a paracrine role for activin in these tumors which may be modulated by follistatin, particularly in the GCT. (C) 1999 Academic Press.