Expression of estrogen receptor (ER) (beta)cx protein in ER(alpha)-positive breast cancer: specific correlation with progesterone receptor.
Estrogen receptor (ER) (beta)cx, a splice variant of ERbeta, is a dominant repressor of ER(alpha) function. In this study we investigated the possibility that because the progesterone receptor (PR) gene is a downstream target of activated ER(alpha), in ER(alpha)-positive breast cancers, expression of ER(beta)cx would result in repression of PR. In ER(alpha)-positive MCF-7 cells, stable transfection of an ER(beta)cx expression vector resulted in reduced expression of PR without affecting ER(alpha) expression. In breast cancers, immunohistochemical evaluation of ER(alpha)-positive foci for the expression of PR and ER(beta)cx revealed a significant correlation between a PR-negative phenotype and the presence of ER(beta)cx within the foci. However, when entire lesions were evaluated by Allred scoring in 115 ER(alpha)-positive breast cancer specimens, the presence of two distinct groups of patients could be discerned. One group expressed ER(beta)cx and had very reduced levels of PR expression, as expected. The second group showed both ER(beta)cx and high levels of PR. To evaluate the role of ER(beta)cx in sensitivity to tamoxifen, 18 core needle biopsies, obtained before preoperative treatment with tamoxifen, were investigated. The results show that expression of ER(beta)cx in primary lesions correlated with a poor response to tamoxifen, especially in cancers with a low PR expression in Allred score. This is the first evidence that evaluation of ER(beta)cx along with PR may contribute to a better characterization of ER(alpha)-positive breast cancers.
Saji
Shigehira
S
Department of Surgery, Breast Oncology Unit, Tokyo Metropolitan Komagome Hospital, 113-8677 Tokyo, Japan. ss-saji@wa2.so-net.ne.jp
Omoto
Yoko
Y
Shimizu
Chikako
C
Warner
Margaret
M
Hayashi
Yukiko
Y
Horiguchi
Shin-ichiro
S
Watanabe
Toru
T
Hayashi
Shin-ichi
S
Gustafsson
Jan-Ake
JA
Toi
Masakazu
M
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D013629:Tamoxifen / Q000627:therapeutic use; D014162:Transfection; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen