Bidirectional interactions between the estrogen receptor and the c-erbB-2 signaling pathways: Heregulin inhibits estrogenic effects in breast cancer cells

T. W. Grunt, M. Saceda, M. B. Martin, Ruth Lupu, E. Dittrich, G. Krupitza, H. Harant, H. Huber, C. Dittrich

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The responsiveness of estrogen receptor (ER)-positive breast cancer to endocrine therapy is frequently reduced in cells over-expressing c-erbB-2. Stimulation of ER suppresses c-erbB-2, indicating that estrogen controls the activity of c-erbB-2. Heregulin (HRG) has been described to bind to c-erbB-3/c-erbB-4 and to stimulate c-erbB-2. Here we describe the effects of HRG on cell growth and on ER and c-erbB-2 expression in breast cancer cell lines containing distinct levels of c-erbB-2 and ER (BT-474: c-erbB-2 +++, ER +; MDA-MB-361: c-erbB-2 ++, ER ++; MCF-7: c-erbB-2 +, ER +++). Proliferation of estrogen-stimulated, c-erbB-2 and ER-positive cells is inhibited by HRG in a dose-dependent manner. In addition, HRG dose-dependently inhibits ER expression. Estrogen, however, inhibits c-erbB-2. Estrogen-mediated down-regulation of c-erbB-2 is most pronounced in MCF-7 but weaker in BT-474. In the latter cells HRG efficiently blocks the estrogenic effect on c-erbB-2. In MCF-7 cells, however, the inhibition of c-erbB-2 cannot be completely reverted by HRG. This modulation occurs in all 3 cell lines at protein, RNA and transcriptional levels, suggesting that the activity of the c-erbB-2 promoter, which contains an estrogen-responsive region, is affected by HRG. The intensity of the mutual inhibition between the HRG/c-erbB-2 and the estrogen/ER system depends on the relative levels of ER and c-erbB-2 expression in the respective cell lines.

Original languageEnglish (US)
Pages (from-to)560-567
Number of pages8
JournalInternational Journal of Cancer
Volume63
Issue number4
DOIs
StatePublished - 1995
Externally publishedYes

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Neuregulin-1
Estrogen Receptors
Estrogens
Breast Neoplasms
ErbB-2 Receptor
Cell Line
MCF-7 Cells
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bidirectional interactions between the estrogen receptor and the c-erbB-2 signaling pathways : Heregulin inhibits estrogenic effects in breast cancer cells. / Grunt, T. W.; Saceda, M.; Martin, M. B.; Lupu, Ruth; Dittrich, E.; Krupitza, G.; Harant, H.; Huber, H.; Dittrich, C.

In: International Journal of Cancer, Vol. 63, No. 4, 1995, p. 560-567.

Research output: Contribution to journalArticle

Grunt, T. W. ; Saceda, M. ; Martin, M. B. ; Lupu, Ruth ; Dittrich, E. ; Krupitza, G. ; Harant, H. ; Huber, H. ; Dittrich, C. / Bidirectional interactions between the estrogen receptor and the c-erbB-2 signaling pathways : Heregulin inhibits estrogenic effects in breast cancer cells. In: International Journal of Cancer. 1995 ; Vol. 63, No. 4. pp. 560-567.
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abstract = "The responsiveness of estrogen receptor (ER)-positive breast cancer to endocrine therapy is frequently reduced in cells over-expressing c-erbB-2. Stimulation of ER suppresses c-erbB-2, indicating that estrogen controls the activity of c-erbB-2. Heregulin (HRG) has been described to bind to c-erbB-3/c-erbB-4 and to stimulate c-erbB-2. Here we describe the effects of HRG on cell growth and on ER and c-erbB-2 expression in breast cancer cell lines containing distinct levels of c-erbB-2 and ER (BT-474: c-erbB-2 +++, ER +; MDA-MB-361: c-erbB-2 ++, ER ++; MCF-7: c-erbB-2 +, ER +++). Proliferation of estrogen-stimulated, c-erbB-2 and ER-positive cells is inhibited by HRG in a dose-dependent manner. In addition, HRG dose-dependently inhibits ER expression. Estrogen, however, inhibits c-erbB-2. Estrogen-mediated down-regulation of c-erbB-2 is most pronounced in MCF-7 but weaker in BT-474. In the latter cells HRG efficiently blocks the estrogenic effect on c-erbB-2. In MCF-7 cells, however, the inhibition of c-erbB-2 cannot be completely reverted by HRG. This modulation occurs in all 3 cell lines at protein, RNA and transcriptional levels, suggesting that the activity of the c-erbB-2 promoter, which contains an estrogen-responsive region, is affected by HRG. The intensity of the mutual inhibition between the HRG/c-erbB-2 and the estrogen/ER system depends on the relative levels of ER and c-erbB-2 expression in the respective cell lines.",
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T2 - Heregulin inhibits estrogenic effects in breast cancer cells

AU - Grunt, T. W.

AU - Saceda, M.

AU - Martin, M. B.

AU - Lupu, Ruth

AU - Dittrich, E.

AU - Krupitza, G.

AU - Harant, H.

AU - Huber, H.

AU - Dittrich, C.

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AB - The responsiveness of estrogen receptor (ER)-positive breast cancer to endocrine therapy is frequently reduced in cells over-expressing c-erbB-2. Stimulation of ER suppresses c-erbB-2, indicating that estrogen controls the activity of c-erbB-2. Heregulin (HRG) has been described to bind to c-erbB-3/c-erbB-4 and to stimulate c-erbB-2. Here we describe the effects of HRG on cell growth and on ER and c-erbB-2 expression in breast cancer cell lines containing distinct levels of c-erbB-2 and ER (BT-474: c-erbB-2 +++, ER +; MDA-MB-361: c-erbB-2 ++, ER ++; MCF-7: c-erbB-2 +, ER +++). Proliferation of estrogen-stimulated, c-erbB-2 and ER-positive cells is inhibited by HRG in a dose-dependent manner. In addition, HRG dose-dependently inhibits ER expression. Estrogen, however, inhibits c-erbB-2. Estrogen-mediated down-regulation of c-erbB-2 is most pronounced in MCF-7 but weaker in BT-474. In the latter cells HRG efficiently blocks the estrogenic effect on c-erbB-2. In MCF-7 cells, however, the inhibition of c-erbB-2 cannot be completely reverted by HRG. This modulation occurs in all 3 cell lines at protein, RNA and transcriptional levels, suggesting that the activity of the c-erbB-2 promoter, which contains an estrogen-responsive region, is affected by HRG. The intensity of the mutual inhibition between the HRG/c-erbB-2 and the estrogen/ER system depends on the relative levels of ER and c-erbB-2 expression in the respective cell lines.

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