Molecular basis of distinct oestrogen responses in endometrial and breast cancer

Endocr Relat Cancer. 2019 Jan 1;26(1):31-46. doi: 10.1530/ERC-17-0563.

Abstract

Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators. We present data on the alternative and novel roles played by SMAD3, CREB-pSer133 and particularly XBP1 in oestrogen signalling in endometrial and breast cancer.

Keywords: CREB; ERα; SMAD3; XBP1; breast cancer; endometrial cancer; oestrogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Endometrial Neoplasms / metabolism*
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, SCID
  • Middle Aged
  • Prognosis
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • X-Box Binding Protein 1 / genetics
  • X-Box Binding Protein 1 / metabolism*

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogens
  • SMAD3 protein, human
  • Smad3 Protein
  • X-Box Binding Protein 1
  • XBP1 protein, human