University of Illinois Chicago
Browse

Gonadotropins Activate Oncogenic Pathways to Enhance Proliferation in Normal Mouse Ovarian Surface Epithelium

Download (1.79 MB)
journal contribution
posted on 2013-12-19, 00:00 authored by Tyvette S. Hilliard, Dimple A. Modi, Joanna E. Burdette
Ovarian cancer is the most lethal gynecological malignancy affecting American women. The gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), have been implicated as growth factors in ovarian cancer. In the present study, pathways activated by FSH and LH in normal ovarian surface epithelium (OSE) grown in their microenvironment were investigated. Gonadotropins increased proliferation in both three-dimensional (3D) ovarian organ culture and in a two-dimensional (2D) normal mouse cell line. A mouse cancer pathway qPCR array using mRNA collected from 3D organ cultures identified Akt as a transcriptionally upregulated target following stimulation with FSH, LH and the combination of FSH and LH. Activation of additional pathways, such as Birc5, Cdk2, Cdk4, and Cdkn2a identified in the 3D organ cultures, were validated by western blot using the 2D cell line. Akt and epidermal growth factor receptor (EGFR) inhibitors blocked gonadotropin-induced cell proliferation in 3D organ and 2D cell culture. OSE isolated from 3D organ cultures stimulated with LH or hydrogen peroxide initiated growth in soft agar. Hydrogen peroxide stimulated colonies were further enhanced when supplemented with FSH. LH colony formation and FSH promotion were blocked by Akt and EGFR inhibitors. These data suggest that the gonadotropins stimulate some of the same proliferative pathways in normal OSE that are activated in ovarian cancers.

Funding

We would like to thank the Ovarian Cancer Research Fund Liz Tilberis Award L/T/UIC/0.1.2011. Joanna E. Burdette, PhD was supported by “The American Cancer Society Illinois Division Research Scholar Grant, RSG-12-230-01-TBG”.

History

Publisher Statement

© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

Publisher

MDPI

Language

  • en_US

issn

1422-0067

Issue date

2013-03-01

Usage metrics

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC