Abstract
The measurement of estrogen receptor (ER) α in breast cancer tissues is important to discriminate between the hormone dependent and independent tumors. Recently, a second ER, referred to as ERβ, has been identified. The DNA binding domain of ERβ is 96% conserved compared with ERα, and the ligand binding domain shows 53% conserved residues, suggesting that both receptors can bind estrogen responsive elements on target genes, and that they may also bind similar ligand. While both receptors bind to 17β-estradiol with equal affinity, other compounds bind with varying affinities to the two receptors. Since the function of ERβ in breast cancer progression is not well understood, further characterization of the function of ERβ and its isoforms in breast cancer is warranted. Various kinds of cofactors, such as steroid receptor coactivator-1 (SRC-1), transcription intermediary factor 2 (TIF2), and amplified in breast cancer 1 (AIB1), have also been reported. These coactivators interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation and recruitment of additional coactivator, such as CREB binding protein (CBP)/p300.
Thus, action of estrogen is not as simple as thought previously, and is likely influenced by ERβ, its variants and interaction with cofactors. Improved understanding of the ER mechanism may follow from the discovery of these proteins, although their precise roles remain to be determined.
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Abbreviations
- ER:
-
Estrogen receptor
- PgR:
-
Progesterone receptor
- AF-1/-2:
-
Activation function-1/-2 domain
- LBD:
-
Ligand binding domain
- ERE:
-
Estrogen responsive element
- TBP:
-
TATA binding protein
- HAT:
-
Histone acetyltransferase
- DRIP:
-
Vitamin D receptor interacting proteins
- CBP:
-
CREB binding protein
- SRC:
-
Steroid receptor coactivator
- TIF2:
-
Transcription intermediary factor 2
- GRIP 1:
-
GR-interacting protein 1
- ACTR:
-
hRARβ-stimulatory protein
- P/CIP:
-
CBP-interacting protein
- RAC3:
-
RAR-interacting protein
- AIB1:
-
Amplified in breast cancer
- SMRT:
-
Silencing mediator for retinoid and thyroid-hormone receptors
- NcoR:
-
Nuclear receptor corepressor
- HDAC:
-
Histone deacethylase
- SERM:
-
Selective estrogen receptor modulator
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Reprint requests to Hirotaka Iwase, Department of Oncology and Endocrinology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan.
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Iwase, H. Molecular action of the estrogen receptor and hormone dependency in breast cancer. Breast Cancer 10, 89–96 (2003). https://doi.org/10.1007/BF02967632
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DOI: https://doi.org/10.1007/BF02967632