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.


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.


CONCLUSIONS
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.
Hoeing
Anna
A
Ludwig-Maximilians University Munich, First Department of Obstetrics and Gynecology, Maistrasse 11, 80337 Munich, Germany.
Kuhn
Christina
C
Shabani
Naim
N
Schulze
Sandra
S
Gingelmaier
Andrea
A
Dian
Darius
D
Jeschke
Udo
U
Friese
Klaus
K
Mylonas
Ioannis
I
D028341:Activins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007265:Inhibins / Q000096:biosynthesis*; D016899:Interferon-beta / Q000378:metabolism*; D015854:Up-Regulation
D028341:Activins; D007265:Inhibins; D016899:Interferon-beta