Differences in expression of proliferation-associated genes and RANKL across the menstrual cycle in estrogen receptor-positive primary breast cancer

Ben P. Haynes, Giuseppe Viale, Viviana Galimberti, Nicole Rotmensz, Bianca Gibelli, Ian E. Smith, Mitch Dowsett

Research output: Contribution to journalArticle

Abstract

The purpose of this study is to determine if there are differences in the expression of estrogen-regulated genes (ERGs), proliferation-associated genes and the progesterone effector RANKL, in premenopausal ER+ breast cancer as a result of the major changes in hormone levels that occur through the menstrual cycle. Primary ER+ tumours from 174 patients were assigned to one of three menstrual cycle windows: W1 (days 27–35 + 1–6), W2 (days 7–16) and W3 (days 17–26). RNA expression of 42 genes, including 24 putative genes associated with plasma E2 levels, seven proliferation genes and RANKL was measured. Expression of PGR, TFF1, GREB1 and PDZK1 followed the previously reported pattern: a higher level in W2 compared to W1 while W3 had an intermediate value, mirroring changes in plasma estradiol. Of the other 20 ERGs, four (RUNX1, AGR2, SERPINA3 and SERPINA5) showed significant differences (p = 0.009–0.049) in expression across the menstrual cycle. The expression of six of seven proliferation-associated genes varied across the cycle but differently from the ERGs, being 20–35 % lower in W3 compared to W1 and W2 (p = 0.004–0.031). Expression of RANKL was 2.5 to 3-fold highest in W3 (p = 0.0001) and negatively correlated to the expression of the proliferation-associated genes (r = −0.37; p 

Original languageEnglish
Pages (from-to)327-335
Number of pages9
JournalBreast Cancer Research and Treatment
Volume148
Issue number2
DOIs
Publication statusPublished - Nov 7 2014

Keywords

  • Estradiol
  • Estrogen receptor
  • Estrogen-regulated
  • Menstrual cycle
  • Premenopausal
  • Progesterone receptor
  • RANKL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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