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

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