title: Effect of luteinizing hormone-induced prohibitin and matrix metalloproteinases on ovarian epithelial tumor cell proliferation.
abstract: Recent studies have suggested that elevated gonadotropins contribute to ovarian epithelial tumor (OET) cell proliferation. However, the cellular effects of luteinizing hormone, a member of gonadotropins, on OET proliferation are controversial. Our previous work showed that luteinizing hormone has no effect on cell proliferation, but the molecular mechanism of such finding remains to be clarified. Considering that the cell growth in various types of tumors has been associated with regulations of prohibitin and matrix metalloproteinases, we aim to investigate a possible regulatory role of luteinizing hormone on prohibitin and matrix metalloproteinases to determine the roles of these molecules in OET proliferation. We found that LH stimulation resulted in a dose-dependent expression of prohibitin and MMPs and time-dependent phosphorylations of ERK and AKT. Blocking MAPK or PI3K/AKT signaling could attenuate LH-induced prohibitin and MMPs expression. Additionally, the depletion of prohibitin reduced the level of MMPs expression, and increased prohibitin expression abolished the positive effect of LH-induced MMP-9 on cellular growth. Therefore, we conclude that LH is able to up-regulate both prohibitin and MMP-9 in OET cells without the cellular growth effect due to opposing biologic functions for cell proliferation between these two molecules. The opposing cellular growth function between prohibitin and MMP-9 is a novel finding. Regulation of either molecule may be useful for future targeted therapy for ovarian epithelial cancers.
authors: Department of Obstetrics and Gynecology, Henan Province People's Hospital Zhengzhou, China ; Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Obstetrics and Gynecology, University of Arizona Tucson, AZ, USA.
authors: Yue
authors: Y
authors: Wang
authors: Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine Shanghai, China ; Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Obstetrics and Gynecology, University of Arizona Tucson, AZ, USA.
authors: Hong
authors: H
authors: Liao
authors: Basis Tucson North High School and University of Arizona Tucson, AZ, USA.
authors: Holly C
authors: HC
authors: Zheng
authors: Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Pathology, Shanxi Medical University Taiyuan, China.
authors: Linmin
authors: L
authors: Li
authors: Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Shandong, China.
authors: Lin
authors: L
authors: Jia
authors: Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Obstetrics and Gynecology, Shanghai First People's Hospital, Shanghai Jiaotong University Shanghai, China.
authors: Zhengbo
authors: Z
authors: Zhang
authors: Department of Pathology, University of Arizona College of Medicine Tucson, AZ, USA ; Department of Obstetrics and Gynecology, University of Arizona Tucson, AZ, USA ; Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Shandong, China ; Arizona Cancer Center, University of Arizona Tucson, AZ, USA.
authors: Wenxin
authors: W
authors: Zheng
keywords: LH; MMP-2; MMP-9; Prohibitin; proliferation
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