Progesterone receptor modulates ERα action in breast cancer

Hisham Mohammed, I. Alasdair Russell, Rory Stark, Oscar M. Rueda, Theresa E. Hickey, Gerard A. Tarulli, Aurelien A A Serandour, Stephen N. Birrell, Alejandra Bruna, Amel Saadi, Suraj Menon, James Hadfield, Michelle Pugh, Ganesh V. Raj, Gordon D. Brown, Clive D'Santos, Jessica L L Robinson, Grace Silva, Rosalind Launchbury, Charles M. PerouJohn Stingl, Carlos Caldas, Wayne D. Tilley, Jason S. Carroll

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα<sup>+</sup> cell line xenografts and primary ERα<sup>+</sup> breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα<sup>+</sup> breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)313-317
Number of pages5
JournalNature
Volume523
Issue number7560
DOIs
StatePublished - Jul 16 2015

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Progesterone Receptors
Breast Neoplasms
Chromatin
Heterografts
Estrogen Receptors
Genes
Progesterone
Estrogens
Biomarkers
Ligands
Gene Expression
Cell Line
Growth
Proteins

ASJC Scopus subject areas

  • General

Cite this

Mohammed, H., Russell, I. A., Stark, R., Rueda, O. M., Hickey, T. E., Tarulli, G. A., ... Carroll, J. S. (2015). Progesterone receptor modulates ERα action in breast cancer. Nature, 523(7560), 313-317. https://doi.org/10.1038/nature14583

Progesterone receptor modulates ERα action in breast cancer. / Mohammed, Hisham; Russell, I. Alasdair; Stark, Rory; Rueda, Oscar M.; Hickey, Theresa E.; Tarulli, Gerard A.; Serandour, Aurelien A A; Birrell, Stephen N.; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V.; Brown, Gordon D.; D'Santos, Clive; Robinson, Jessica L L; Silva, Grace; Launchbury, Rosalind; Perou, Charles M.; Stingl, John; Caldas, Carlos; Tilley, Wayne D.; Carroll, Jason S.

In: Nature, Vol. 523, No. 7560, 16.07.2015, p. 313-317.

Research output: Contribution to journalArticle

Mohammed, H, Russell, IA, Stark, R, Rueda, OM, Hickey, TE, Tarulli, GA, Serandour, AAA, Birrell, SN, Bruna, A, Saadi, A, Menon, S, Hadfield, J, Pugh, M, Raj, GV, Brown, GD, D'Santos, C, Robinson, JLL, Silva, G, Launchbury, R, Perou, CM, Stingl, J, Caldas, C, Tilley, WD & Carroll, JS 2015, 'Progesterone receptor modulates ERα action in breast cancer', Nature, vol. 523, no. 7560, pp. 313-317. https://doi.org/10.1038/nature14583
Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA et al. Progesterone receptor modulates ERα action in breast cancer. Nature. 2015 Jul 16;523(7560):313-317. https://doi.org/10.1038/nature14583
Mohammed, Hisham ; Russell, I. Alasdair ; Stark, Rory ; Rueda, Oscar M. ; Hickey, Theresa E. ; Tarulli, Gerard A. ; Serandour, Aurelien A A ; Birrell, Stephen N. ; Bruna, Alejandra ; Saadi, Amel ; Menon, Suraj ; Hadfield, James ; Pugh, Michelle ; Raj, Ganesh V. ; Brown, Gordon D. ; D'Santos, Clive ; Robinson, Jessica L L ; Silva, Grace ; Launchbury, Rosalind ; Perou, Charles M. ; Stingl, John ; Caldas, Carlos ; Tilley, Wayne D. ; Carroll, Jason S. / Progesterone receptor modulates ERα action in breast cancer. In: Nature. 2015 ; Vol. 523, No. 7560. pp. 313-317.
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