Estrogen receptor β exerts tumor repressive functions in human malignant pleural mesothelioma via EGFR inactivation and affects response to Gefitinib

53Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

Abstract

Background: The role of estrogen and estrogen receptors in oncogenesis has been investigated in various malignancies. Recently our group identified estrogen receptor beta (ERβ) expression as an independent prognostic factor in the progression of human Malignant Pleural Mesothelioma (MMe), but the underlying mechanism by which ERβ expression in tumors determines clinical outcome remains largely unknown. This study is aimed at investigating the molecular mechanisms of ERβ action in MMe cells and disclosing the potential translational implications of these results. Methods: We modulated ERβ expression in REN and MSTO-211H MMe cell lines and evaluated cell proliferation and EGF receptor (EGFR) activation. Results: Our data indicate that ERβ knockdown in ER positive cells confers a more invasive phenotype, increases anchorage independent proliferation and elevates the constitutive activation of EGFR-coupled signal transduction pathways. Conversely, re-expression of ERβ in ER negative cells confers a more epithelioid phenotype, decreases their capacity for anchorage independent growth and down-modulates proliferative signal transduction pathways. We identify a physical interaction between ERβ, EGFR and caveolin 1 that results in an altered internalization and in a selective reduced activation of EGFR-coupled signaling, when ERβ is over-expressed. We also demonstrate that differential expression of ERβ influences MMe tumor cell responsiveness to the therapeutic agent: Gefitinib. Conclusions: This study describes a role for ERβ in the modulation of cell proliferation and EGFR activation and provides a rationale to facilitate the targeting of a subgroup of MMe patients who would benefit most from therapy with Gefitinib alone or in combination with Akt inhibitors. © 2010 Pinton et al.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Pinton, G., Thomas, W., Bellini, P., Manente, A. G., Favoni, R. E., Harvey, B. J., … Moro, L. (2010). Estrogen receptor β exerts tumor repressive functions in human malignant pleural mesothelioma via EGFR inactivation and affects response to Gefitinib. PLoS ONE, 5(11). https://doi.org/10.1371/journal.pone.0014110

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

56%

Researcher 4

25%

Professor / Associate Prof. 3

19%

Readers' Discipline

Tooltip

Medicine and Dentistry 7

44%

Agricultural and Biological Sciences 5

31%

Pharmacology, Toxicology and Pharmaceut... 2

13%

Biochemistry, Genetics and Molecular Bi... 2

13%

Save time finding and organizing research with Mendeley

Sign up for free