The measurement of
estrogen receptor (ER)alpha in
breast cancer tissues is important to discriminate between the
hormone dependent and independent
tumors. Recently, a second ER, referred to as
ERbeta, has been identified. The
DNA binding domain of
ERbeta is 96% conserved compared with
ERalpha, 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 17beta-estradiol with equal affinity, other compounds bind with varying affinities to the two receptors. Since the function of
ERbeta in
breast cancer progression is not well understood, further characterization of the function of
ERbeta 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
ERbeta, 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.