The immunohistochemical expression of the inhibin/activin subunits is up-regulated by interferon-beta1a in Ishikawa cell line.

Background: Inhibins are dimeric glycoproteins belonging to the TGF-beta1 family and are composed of an a-subunit (INH-alpha) and one of two possible beta-subunits (betaA or betaB; INH-betaA and INH-betaB). They have a substantial function in human reproduction and also seem to play an important role in endocrine-responsive tumors. Interestingly, there is an association between interferon and TGF-beta expression. However, this relationship has not been assessed in endometrial tissue regarding inhibin/activin expression. Therefore, the aim of this study was to determine expression changes of inhibin/activin subunits in the endometrial Ishikawa carcinoma cell line after stimulation with interferon-beta1a.

Materials And Methods: The Ishikawa cell line was cultured until confluence was observed (after 2 days). After adding interferon-beta1a (1000 IE/ml) Ishikawa cells were immunohistochemical analyzed for INH-alpha, INH-betaA and INH-betaB subunits. Experiments were performed in triplicates. The immunohistochemical expression was analyzed with a semiquantitative score (IRS) and statistical analysis was performed.

Results: Immunohistochemical reaction with INH-alpha could not be demonstrated in unstimulated cells, while it was significantly up-regulated in interferon-stimulated cells (p < 0.02). INH-betaA and INH-betaB were primarily observed during the mitotic phases of unstimulated cells. After stimulation their expression was significantly higher (p < 0.05 each) compared to controls and could be observed not only during mitotic phases but also in nonmitotic cells.

Conclusion: For the first time, we demonstrated a functional relationship between interferon and inhibin/activin subunits. The expression of INH-alpha, INH-betaA and INH-betaB were immunohistochemical significantly up-regulated in the Ishikawa endometrial cell line after stimulation with interferon-beta1a. Since INH-alpha is thought to be tumor suppressive in the mouse model, interferon-beta1a might activate its gene. It remains to be clarified if this effect can be used as therapeutic options in endometrial carcinomas.