Estrogen-independent role of ERalpha in ovarian cancer progression induced by leptin/Ob-Rb axis

(2019) Estrogen-independent role of ERalpha in ovarian cancer progression induced by leptin/Ob-Rb axis. Mol Cell Biochem. ISSN 1573-4919 (Electronic) 0300-8177 (Linking)

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Abstract

Leptin induces ovarian cancer cell invasion via overexpression of MMP7, MMP9, and upA. In addition, the key role of ERalpha in leptin-increased cell growth was indicated. However, the influence of ER on leptin-mediated cell invasion remains still unknown. The present study was designed to evaluate the E2-independent effect of ERalpha/beta on leptin-mediated cell invasion and cell proliferation in ovarian cancer. We utilized SKOV3 cancer (expressing OB-Rb and ERalpha/beta, insensitive to estrogen) and OVCAR3 (expressing OB-Rb) cell lines to show the involvement of ER in leptin-mediated effects in an E2-independent manner. MTT, BrdU, and BD matrigel invasion assays were applied to analyze cell growth, proliferation, and invasion. The siRNA approach was used to confirm the role of ERalpha/beta in leptin effects. Moreover, western blotting and Real-time PCR were employed to detect the OB-Rb, ER, MMP9/7, and upA proteins and mRNAs. Leptin, in the absence of E2, increased ERalpha expression in SKOV3 cells, which was attenuated using knockdown of OB-Rb gene by siRNA. The effect of leptin on the cell growth was promoted in the presence of PPT, but not in the presence of DNP and E2, which was lost when OB-Rb siRNA was transfected. Furthermore, ERalpha gene silencing and/or pre-incubation with ER antagonist (ICI 182,780, 10 nM) significantly reduced cell invasion and MMP9 expression stimulated by leptin. In conclusion, our findings demonstrated that ERalpha, but not ERbeta, is involved in leptin-induced ovarian cancer in an E2-independent manner, providing new evidence for cancer progression in obesity-associated ovarian cancer.

Item Type: Article
Keywords: Cell invasion Estradiol Estrogen receptor Leptin Ovarian cancer
Subjects: QZ Pathology > QZ 200-380 Neoplasms
QZ Pathology > QZ 40-105 Pathogenesis. Etiology
WP Gynecology and Obstetrics > WP 650-660 Therapy
Divisions: Faculty of Pharmacy and Pharmaceutical Sciences > Department of Clinical Biochemistry
Journal or Publication Title: Mol Cell Biochem
Journal Index: Pubmed
Identification Number: https://doi.org/10.1007/s11010-019-03544-5
ISSN: 1573-4919 (Electronic) 0300-8177 (Linking)
Depositing User: Zahra Otroj
URI: http://eprints.mui.ac.ir/id/eprint/10547

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