Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines

Miguel Saceda, Thomas W. Grunt, Ramon Colomer, Marc E Lippman, Ruth Lupu, Mary Beth Martin

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Expression of the erbB-2 oncogene in breast cancer patients correlates with pear prognosis and failure of hormonal therapy. In this study, the effects of a putative erbB/HER ligand, gp30, on estrogen receptor (ER) concentration and activity was investigated in the estrogen receptor positive human breast cancer cells, BT474 and MCF-7, which express either high or low levels of erbB-2 and erbB-4, respectively. Treatment of cells with gp30 resulted in a decrease in the steady-state level of estrogen receptor protein by approximately 70-80%. The effect of gp30 on the concentration of ER was independent of serum in the media and was not inhibited by an epidermal growth flitter receptor blocking antibody. In addition to the effect on ER protein, gp30 decreased the steady-state level of ER messenger RNA. Transcription run on experiments demonstrated that the decrease in ER expression was mediated by a decrease in ER gene transcription. The effect of gp30 on estrogen receptor activity was also investigated in this study. Treatment of cells with gp30 blocked estradiol induction of progesterone receptor. Inhibition was observed at the level of progesterone receptor protein, messenger RNA, and gene transcription. gp30 also blocked estradiol induction of pS2 gene transcription. In addition to its effects on progesterone receptor and pS2, gp30 blocked activation of an estrogen response element in a transient transfection assay and inhibited ER binding to its response element in a DNA mobility shift assay, suggesting a direct effect on the estrogen receptor. The effects of gp30 on estrogen receptor concentration and activity were independent of the level of erbB-2 and erbB- 4 in the cell. These data show that gp30 regulates the concentration of ER and modulates ER activity.

Original languageEnglish
Pages (from-to)4322-4330
Number of pages9
JournalEndocrinology
Volume137
Issue number10
DOIs
StatePublished - Oct 7 1996
Externally publishedYes

Fingerprint

Estrogen Receptors
Breast Neoplasms
Ligands
Cell Line
Progesterone Receptors
Response Elements
Estradiol
Genes
Pyrus
Messenger RNA
Blocking Antibodies
MCF-7 Cells
Electrophoretic Mobility Shift Assay
Oncogenes
Transfection
Estrogens
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Saceda, M., Grunt, T. W., Colomer, R., Lippman, M. E., Lupu, R., & Martin, M. B. (1996). Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines. Endocrinology, 137(10), 4322-4330. https://doi.org/10.1210/en.137.10.4322

Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines. / Saceda, Miguel; Grunt, Thomas W.; Colomer, Ramon; Lippman, Marc E; Lupu, Ruth; Martin, Mary Beth.

In: Endocrinology, Vol. 137, No. 10, 07.10.1996, p. 4322-4330.

Research output: Contribution to journalArticle

Saceda, M, Grunt, TW, Colomer, R, Lippman, ME, Lupu, R & Martin, MB 1996, 'Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines', Endocrinology, vol. 137, no. 10, pp. 4322-4330. https://doi.org/10.1210/en.137.10.4322
Saceda, Miguel ; Grunt, Thomas W. ; Colomer, Ramon ; Lippman, Marc E ; Lupu, Ruth ; Martin, Mary Beth. / Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines. In: Endocrinology. 1996 ; Vol. 137, No. 10. pp. 4322-4330.
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