17β-Estradiol Sensitizes Ovarian Surface Epithelium to Transformation by Suppressing Disabled-2 Expression

Overview

Journal Sci Rep

Specialty Science

Date 2017 Dec 3

PMID 29196616

Citations 8

Authors

Nhung H Vuong

Omar Salah Salah

Barbara C Vanderhyden

Affiliations

Soon will be listed here.

Abstract

Estrogen replacement therapy increases the risk of human ovarian cancer and exogenous estradiol accelerates the onset of ovarian cancer in mouse models. This study uses primary cultures of mouse ovarian surface epithelium (OSE) to demonstrate that one possible mechanism by which estrogen accelerates the initiation of ovarian cancer is by up-regulation of microRNA-378 via the ESR1 pathway to result in the down-regulation of a tumour suppressor called Disabled-2 (Dab2). Estrogen suppression of Dab2 was reproducible in vivo and across many cell types including mouse oviductal epithelium and primary cultures of human ovarian cancer cells. Suppression of Dab2 resulted in increased proliferation, loss of contact inhibition, morphological dysplasia, and resistance to oncogene-induced senescence - all factors that can sensitize OSE to transformation. Given that DAB2 is highly expressed in healthy human OSE and is absent in the majority of ovarian tumours, this study has taken the first steps to provide a mechanistic explanation for how estrogen therapy may play a role in the initiation of ovarian cancer.

Citing Articles

The scaffold protein disabled 2 (DAB2) and its role in tumor development and progression.

Pandya D, Parikh R, Gena R, Kothari N, Parekh P, Chorawala M Mol Biol Rep. 2024; 51(1):701.

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AMPK-upregulated microRNA-708 plays as a suppressor of cellular senescence and aging via downregulating disabled-2 and mTORC1 activation.

Zhang J, Gong H, Zhao T, Xu W, Chen H, Li T MedComm (2020). 2024; 5(3):e475.

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Disabled-2 (): A Key Regulator of Anti- and Pro-Tumorigenic Pathways.

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Microscopic Evaluation of Ovarian Surface Epithelium Following Treatment with Conjugated Estrogens in a Mouse Model.

Al-Amri I, Kadim I, Al-Kindi A, Khalaf S, Al-Harrasi A, Al-Hashmi S Asian Pac J Cancer Prev. 2022; 23(6):1913-1920.

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