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Title: Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells

Abstract

Highlights: Black-Right-Pointing-Pointer TTF-2 was expressed in mammary glands and breast cancer cells. Black-Right-Pointing-Pointer TTF-2 repressed ER{alpha} transactivation. Black-Right-Pointing-Pointer TTF-2 inhibited the proliferation of breast cancer cells. -- Abstract: Estrogen receptors (ERs), which mediate estrogen actions, regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors through interaction with cellular factors. In this study, we show that thyroid transcription factor-2 (TTF-2) is expressed in mammary gland and acts as ER{alpha} co-repressor. TTF-2 inhibited ER{alpha} transactivation in a dose-dependent manner in MCF-7 breast cancer cells. In addition, TTF-2 directly bound to and formed a complex with ER{alpha}, colocalizing with ER{alpha} in the nucleus. In MCF-7/TTF-2 stable cell lines, TTF-2 repressed the expression of endogenous ER{alpha} target genes such as pS2 and cyclin D1 by interrupting ER{alpha} binding to target promoters and also significantly decreased cell proliferation. Taken together, these data suggest that TTF-2 may modulate the function of ER{alpha} as a corepressor and play a role in ER-dependent proliferation of mammary cells.

Authors:
;  [1];  [2];  [1]
  1. Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of)
  2. Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie 8, 37134 Verona (Italy)
Publication Date:
OSTI Identifier:
22207846
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 421; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL PROLIFERATION; ESTRADIOL; INHIBITION; MAMMARY GLANDS; NEOPLASMS; PROMOTERS; RECEPTORS; THYROID; TRANSCRIPTION FACTORS

Citation Formats

Park, Eunsook, Gong, Eun-Yeung, Romanelli, Maria Grazia, and Lee, Keesook, E-mail: klee@chonnam.ac.kr. Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.04.039.
Park, Eunsook, Gong, Eun-Yeung, Romanelli, Maria Grazia, & Lee, Keesook, E-mail: klee@chonnam.ac.kr. Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells. United States. doi:10.1016/J.BBRC.2012.04.039.
Park, Eunsook, Gong, Eun-Yeung, Romanelli, Maria Grazia, and Lee, Keesook, E-mail: klee@chonnam.ac.kr. 2012. "Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells". United States. doi:10.1016/J.BBRC.2012.04.039.
@article{osti_22207846,
title = {Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells},
author = {Park, Eunsook and Gong, Eun-Yeung and Romanelli, Maria Grazia and Lee, Keesook, E-mail: klee@chonnam.ac.kr},
abstractNote = {Highlights: Black-Right-Pointing-Pointer TTF-2 was expressed in mammary glands and breast cancer cells. Black-Right-Pointing-Pointer TTF-2 repressed ER{alpha} transactivation. Black-Right-Pointing-Pointer TTF-2 inhibited the proliferation of breast cancer cells. -- Abstract: Estrogen receptors (ERs), which mediate estrogen actions, regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors through interaction with cellular factors. In this study, we show that thyroid transcription factor-2 (TTF-2) is expressed in mammary gland and acts as ER{alpha} co-repressor. TTF-2 inhibited ER{alpha} transactivation in a dose-dependent manner in MCF-7 breast cancer cells. In addition, TTF-2 directly bound to and formed a complex with ER{alpha}, colocalizing with ER{alpha} in the nucleus. In MCF-7/TTF-2 stable cell lines, TTF-2 repressed the expression of endogenous ER{alpha} target genes such as pS2 and cyclin D1 by interrupting ER{alpha} binding to target promoters and also significantly decreased cell proliferation. Taken together, these data suggest that TTF-2 may modulate the function of ER{alpha} as a corepressor and play a role in ER-dependent proliferation of mammary cells.},
doi = {10.1016/J.BBRC.2012.04.039},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 421,
place = {United States},
year = 2012,
month = 5
}
  • Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 andmore » HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.« less
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