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Scientific article
English

Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF

Published inEMBO journal, vol. 28, no. 5, p. 523-532
Publication date2009
Abstract

The steroid hormone oestrogen can signal through several receptors and pathways. Although the transcriptional responses mediated by the nuclear oestrogen receptors (ER) have been extensively characterized, the changes in gene expression elicited by signalling through the membrane-associated ER GPR30 have not been studied. We show here for ER-negative human breast cancer cells that the activation of GPR30 signalling by oestrogen or by hydroxytamoxifen (OHT), an ER antagonist but GPR30 agonist, induces a transcription factor network, which resembles that induced by serum in fibroblasts. The most strongly induced gene, CTGF, appears to be a target of these transcription factors. We found that the secreted factor connective tissue growth factor (CTGF) not only contributes to promote proliferation but also mediates the GPR30-induced stimulation of cell migration. These results provide a framework for understanding the physiological and pathological functions of GPR30. As the activation of GPR30 by OHT also induces CTGF in fibroblasts from breast tumour biopsies, these pathways may be involved in promoting aggressive behaviour of breast tumours in response to endogenous oestrogens or to OHT being used for endocrine therapy.

Keywords
  • Breast Neoplasms/metabolism/pathology
  • Cell Movement/drug effects/physiology
  • Cell Proliferation/drug effects
  • Connective Tissue Growth Factor/physiology
  • Estrogens/pharmacology
  • Fibroblasts/drug effects/physiology
  • Humans
  • Receptors, Estrogen/antagonists & inhibitors/metabolism
  • Receptors, G-Protein-Coupled/agonists/physiology
  • Signal Transduction/physiology
  • Tamoxifen/analogs & derivatives/pharmacology
  • Tumor Cells, Cultured
Citation (ISO format)
PANDEY, Deo Prakash et al. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. In: EMBO journal, 2009, vol. 28, n° 5, p. 523–532. doi: 10.1038/emboj.2008.304
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Article (Submitted version)
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Article (Accepted version)
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Identifiers
ISSN of the journal0261-4189
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Creation10/13/2009 10:41:00 AM
First validation10/13/2009 10:41:00 AM
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