The re-expression of estrogen receptor in estrogen receptor-negative breast cancer and restoration of anti-estrogen responses

Jill Bayliss, Amy Hilger, Prakash Vishnu, Kathleen Diehl, Dorraya El-Ashry

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Loss of estrogen receptor α ERα in breast cancer correlates with a more aggressive, tamoxifen resistant phenotype. ERα-negative tumors often display overexpression or amplification of growth factor receptors of the erbB family, particularly EGFR and erbB-2, and consequently, elevated growth factor signaling and resultant MAP kinase (ERK) activity. We have previously shown that overexpression/hyperactivation of EGFR or erbB-2, or the downstream effectors Raf or MEK, in ERα+, estrogen-dependent MCF-7 cells results in the acquisition of estrogen-independence and loss of ERα expression. We have shown that the common downstream effector of ERα downregulation in all our model cell lines is hyperactive MAPK and that inhibition of this hyperactive MAPK restores ERα expression. Microarray expression profiling of these hyperactive MAPK model cell lines revealed a hyperactive MAPK signature that correlates with ERα-breast cancer and not ERα+ breast cancer. We have more recently extended these observations to established ERα-breast cancer cell lines and primary cultures from ERα-breast tumor specimens. Inhibition of MAPK in these ERα-breast cancer cells restores ERα expression and associated with this re-expression of ERα is the acquisition of anti-estrogen responses. These data demonstrate the dynamic nature of ERα expression in breast cancer cells and the ability to impact ERα expression by altering cellular signaling pathways. Further, they suggest a potential novel therapeutic strategy for ERα-breast cancer: inhibition of MAPK activity to restore both ERα expression and anti-estrogen responses.

Original languageEnglish (US)
Title of host publicationTherapeutic Resistance to Anti-Hormonal Drugs in Breast Cancer
Subtitle of host publicationNew Molecular Aspects and their Potential as Targets
PublisherSpringer Netherlands
Pages39-61
Number of pages23
ISBN (Print)9781402085253
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Estrogen receptor loss
  • MAPK
  • Microarray profiling

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bayliss, J., Hilger, A., Vishnu, P., Diehl, K., & El-Ashry, D. (2009). The re-expression of estrogen receptor in estrogen receptor-negative breast cancer and restoration of anti-estrogen responses. In Therapeutic Resistance to Anti-Hormonal Drugs in Breast Cancer: New Molecular Aspects and their Potential as Targets (pp. 39-61). Springer Netherlands. https://doi.org/10.1007/978-1-4020-8526-0_3