Expression and regulation of estrogen receptor ß in human breast tumors and cell lines

E. A. Vladusic, A. E. Hornby, F. K. Guerra-Vladusic, J. Lakins, Ruth Lupu

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Expression of estrogen receptor ß(ER-ß) and its regulation by estradiol and anti-estrogens was analyzed in breast cancer cells. We determined that ER-ß is expressed in normal and tumor human breast tissue as well as in breast cancer cell lines. We observed moderate levels of ER-ß expression in both T47D and T47D-V22 (a T47D variant cell line) cells, in contrast with T47DCo (a T47D variant cell line) cells when compared to ER-α expression. While T47DCo (a T47D variant cell line), BT474, MDA-MB-231, MDA-MB-453, MDA-MB-468 and MCF-7 express low levels of ER-ß, other cell lines including the T47D-Y (a T47D variant cell line), MDA-MB-435, BT-549, and SKBr-3 cells express undetectable levels of ER-ß. Interestingly, ER-ß and ER-α are apparently not co-expressed in the breast tissue analyzed. Estradiol induced 30-40-fold increased ER-ß mRNA expression in T47D cells over control untreated cells. Moreover, the anti-estrogen, 4-hydroxy-tamoxifen (4OH-Tam) strongly inhibited estradiol induction of ER-ß expression, but had little or no effect on estradiol induction of ER-α. A pure anti-estrogen, ICI-182,780, completely abolished the ability of estradiol to up-regulate the expression of ER. In addition, both actinomycin D and cyclohexymide inhibited estradiol induction of ER-ß mRNA, indicating that de novo mRNA and protein synthesis are probably required for this induction. In summary, this study demonstrates that ER-ß is expressed in breast cancer, and it is regulated by estradiol. Moreover, the studies demonstrate that estradiol up-regulation of ER-ß mRNA in T47D cells can be abolished by anti-estrogens. Thus, ER-ß expression may serve as a prognostic, diagnostic and/or therapeutic marker for breast cancer. To the best of our knowledge, this is the first report regarding hormonal regulation of ER-ß in human mammary cells.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalOncology Reports
Volume7
Issue number1
StatePublished - 2000
Externally publishedYes

Fingerprint

Tumor Cell Line
Estrogen Receptors
Breast Neoplasms
Estradiol
Cell Line
Estrogens
Messenger RNA
Breast
Up-Regulation
Dactinomycin

Keywords

  • Breast
  • Estradiol
  • Estrogen receptor ß
  • ICI-182,780
  • Regulation
  • Tamoxifen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vladusic, E. A., Hornby, A. E., Guerra-Vladusic, F. K., Lakins, J., & Lupu, R. (2000). Expression and regulation of estrogen receptor ß in human breast tumors and cell lines. Oncology Reports, 7(1), 157-167.

Expression and regulation of estrogen receptor ß in human breast tumors and cell lines. / Vladusic, E. A.; Hornby, A. E.; Guerra-Vladusic, F. K.; Lakins, J.; Lupu, Ruth.

In: Oncology Reports, Vol. 7, No. 1, 2000, p. 157-167.

Research output: Contribution to journalArticle

Vladusic, EA, Hornby, AE, Guerra-Vladusic, FK, Lakins, J & Lupu, R 2000, 'Expression and regulation of estrogen receptor ß in human breast tumors and cell lines', Oncology Reports, vol. 7, no. 1, pp. 157-167.
Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lakins J, Lupu R. Expression and regulation of estrogen receptor ß in human breast tumors and cell lines. Oncology Reports. 2000;7(1):157-167.
Vladusic, E. A. ; Hornby, A. E. ; Guerra-Vladusic, F. K. ; Lakins, J. ; Lupu, Ruth. / Expression and regulation of estrogen receptor ß in human breast tumors and cell lines. In: Oncology Reports. 2000 ; Vol. 7, No. 1. pp. 157-167.
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abstract = "Expression of estrogen receptor {\ss}(ER-{\ss}) and its regulation by estradiol and anti-estrogens was analyzed in breast cancer cells. We determined that ER-{\ss} is expressed in normal and tumor human breast tissue as well as in breast cancer cell lines. We observed moderate levels of ER-{\ss} expression in both T47D and T47D-V22 (a T47D variant cell line) cells, in contrast with T47DCo (a T47D variant cell line) cells when compared to ER-α expression. While T47DCo (a T47D variant cell line), BT474, MDA-MB-231, MDA-MB-453, MDA-MB-468 and MCF-7 express low levels of ER-{\ss}, other cell lines including the T47D-Y (a T47D variant cell line), MDA-MB-435, BT-549, and SKBr-3 cells express undetectable levels of ER-{\ss}. Interestingly, ER-{\ss} and ER-α are apparently not co-expressed in the breast tissue analyzed. Estradiol induced 30-40-fold increased ER-{\ss} mRNA expression in T47D cells over control untreated cells. Moreover, the anti-estrogen, 4-hydroxy-tamoxifen (4OH-Tam) strongly inhibited estradiol induction of ER-{\ss} expression, but had little or no effect on estradiol induction of ER-α. A pure anti-estrogen, ICI-182,780, completely abolished the ability of estradiol to up-regulate the expression of ER. In addition, both actinomycin D and cyclohexymide inhibited estradiol induction of ER-{\ss} mRNA, indicating that de novo mRNA and protein synthesis are probably required for this induction. In summary, this study demonstrates that ER-{\ss} is expressed in breast cancer, and it is regulated by estradiol. Moreover, the studies demonstrate that estradiol up-regulation of ER-{\ss} mRNA in T47D cells can be abolished by anti-estrogens. Thus, ER-{\ss} expression may serve as a prognostic, diagnostic and/or therapeutic marker for breast cancer. To the best of our knowledge, this is the first report regarding hormonal regulation of ER-{\ss} in human mammary cells.",
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