Prohibitin: targeting peptide coupled to ovarian cancer, luteinization and TGF-β pathways

Abstract

Background: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-β has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-β and LH in ovarian cancer.

Methods: The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-β serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively.

Results: Serum levels of LH and TGF-β were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors.

Conclusion: Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-β. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.

Keywords: LH; LHRmRNA; Ovarian epithelial tumor; Prohibitin; TGF-β.

Fig. 1

RT-PCR amplification blot showing expression of LHRmRNA and GAPDH in the studied groups

Fig. 2

Prohibtin expression in normal ovarian tissue showing mild cytoplasmic staining of the luteinized cells lining follicular cyst (IHC; × 40)

Fig. 3

a Prohibtin expression in benign papillary serous cystadenoma. (IHC; ×40). b Prohibitin expression in benign mucinous cystadenoma.(IHC; ×40)

Fig. 4

a Prohibitin expression in borderline serous tumor. (IHC; ×40). b Expression of prohibitin in borderline mucinous tumor. (IHC; ×40)

Fig. 5

a Prohibitin expression in malignant papillary serous cystadenocarcinoma. (IHC; ×40). b Prohibitin expression in malignant mucinous cystadenocacinoma. (IHC; ×40). c Prohibitin expression in malignant endometrioid carcinoma (IHC; ×40). d Prohibitin expression in poorly differentiated carcinoma (IHC; ×40)