Immunolabeling of the Inhibin-βA and -βB Subunit in Normal and Malignant Human Cervical Tissue and Cervical Cancer Cell Lines

Abstract

Inhibins, dimeric peptide hormones composed of an α-subunit and 1 of 2 possible β subunits (βA or βB), exhibit substantial roles in human reproduction and in endocrine-responsive tumors. However, it is still unclear whether normal and cancerous cervical tissues as well as cervical cancer cell lines express the inhibin-βA and -βB subunits. Normal human uterine cervical tissue was obtained from 4 premenopausal nonpregnant patients. In addition, a total of 32 specimens of cervical intraepithelial neoplasia (CIN) of different stages were obtained (CIN 1 = 10, CIN 2 = 9, and CIN 3 = 13). Moreover, 30 squamous cervical cancer samples of well-differentiated (grade 1; n = 10), moderate differentiated (grade 2; n = 10), and poorly differentiated (grade 3; n = 10) grading were analyzed. An immunohistochemical staining reaction for inhibin-βA and -βB subunits could be observed in normal and malignant cervical tissue as well as in cervical cancer cell lines. Regarding inhibin-βA significant differences were observed between normal tissue and CIN 1 and CIN 3. Moreover, the immunohistochemical staining reaction for inhibin-βA was significantly higher in CIN 3 compared with that in cervical carcinoma grades 1 and 2. The inhibin-βB expression was higher in CIN and cervical cancer compared with that in normal cervical tissue. Inhibin-βB was significantly higher in CIN 2 and CIN 3 compared with cancer tissues of histological grade 1. In addition, a significant increase of the staining intensity was observed between cervical cancer grades 1 and 2 as well as grade 3. Both inhibin-β subunits demonstrated a differential expression in CIN and squamous cancer, suggesting important roles in cervical carcinogenesis. Inhibin-βA might be important during progression of CIN, whereas the inhibin-βB subunit could exert a substantial function during differentiation of cervical carcinomas. Moreover, the synthesis of this subunit in cervical carcinoma cell lines also allows the use of this cell line to elucidates their functions in cervical cancer pathogenesis.