Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells

Madeline M Keenen,1 Suwon Kim1,2 1Department of Basic Medical Sciences, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 2Division of Cancer and Cell Biology, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Resistance to antiestrogen therapy remains a...

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Autores principales:	Keenen MM, Kim S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	ING4 tumor suppressor estrogen receptor breast cancer tamoxifen resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/461a180658264d96acad0768a734ce04
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spelling	oai:doaj.org-article:461a180658264d96acad0768a734ce042021-12-02T00:48:28ZTumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells1179-1314https://doaj.org/article/461a180658264d96acad0768a734ce042016-11-01T00:00:00Zhttps://www.dovepress.com/tumor-suppressor-ing4-inhibits-estrogen-receptor-activity-in-breast-ca-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Madeline M Keenen,1 Suwon Kim1,2 1Department of Basic Medical Sciences, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 2Division of Cancer and Cell Biology, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose–response of estrogen. These results indicated that ING4 functions as a noncompetitive inhibitor of estrogen signaling and may inhibit estrogen-independent ER activity. Supportive of this, treatment with fulvestrant but not tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4 overexpression. ING4 did not affect nuclear ERα protein expression, but repressed selective ER-target gene transcription. Taken together, these results demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting that ING4-low breast tumors recur faster due to estrogen-independent ER activity that renders tamoxifen less effective. This study puts forth fulvestrant as a proposed therapy choice for patients with ING4-low ER+ breast tumors. Keywords: tamoxifen resistance, transcription repression, PDZK1, TFF1, estrogen independent ERa, fulvestrant  Keenen MMKim SDove Medical PressarticleING4tumor suppressorestrogen receptorbreast cancertamoxifen resistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 8, Pp 211-221 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	ING4 tumor suppressor estrogen receptor breast cancer tamoxifen resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ING4 tumor suppressor estrogen receptor breast cancer tamoxifen resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Keenen MM Kim S Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
description	Madeline M Keenen,1 Suwon Kim1,2 1Department of Basic Medical Sciences, University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 2Division of Cancer and Cell Biology, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose–response of estrogen. These results indicated that ING4 functions as a noncompetitive inhibitor of estrogen signaling and may inhibit estrogen-independent ER activity. Supportive of this, treatment with fulvestrant but not tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4 overexpression. ING4 did not affect nuclear ERα protein expression, but repressed selective ER-target gene transcription. Taken together, these results demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting that ING4-low breast tumors recur faster due to estrogen-independent ER activity that renders tamoxifen less effective. This study puts forth fulvestrant as a proposed therapy choice for patients with ING4-low ER+ breast tumors. Keywords: tamoxifen resistance, transcription repression, PDZK1, TFF1, estrogen independent ERa, fulvestrant
format	article
author	Keenen MM Kim S
author_facet	Keenen MM Kim S
author_sort	Keenen MM
title	Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
title_short	Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
title_full	Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
title_fullStr	Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
title_full_unstemmed	Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells
title_sort	tumor suppressor ing4 inhibits estrogen receptor activity in breast cancer cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/461a180658264d96acad0768a734ce04
work_keys_str_mv	AT keenenmm tumorsuppressoring4inhibitsestrogenreceptoractivityinbreastcancercells AT kims tumorsuppressoring4inhibitsestrogenreceptoractivityinbreastcancercells
_version_	1718403434328096768

Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells

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