Distinct mechanisms of oestrogen signalling in endometrial cancer
The action of oestrogen via its receptors is important in the pathophysiology of both endometrial and breast cancer. Oestrogen receptor-α (ERα) is expressed in up to 80% of breast and endometrial cancers, but anti-oestrogen therapy is effective in breast but not endometrial cancer. To assess potential differences, Baxter et al. used data from The Cancer Genome Atlas (TCGA), in conjunction with cell line studies, to investigate the molecular mechanisms of oestrogen signalling in endometrial and breast cancers.
Phosphorylation of ERα at serine residue 118 (ERα-pSer118) was found to be prognostic for endometrial but not breast cancer in TCGA data. High ERα-pSer118 levels were associated with significantly worse progression-free survival and poorer overall survival in endometrial cancer. Gene expression profile analysis demonstrated that ERα-associated networks were distinct between tumour types. ERα co-regulators, including FOXA1 and GATA3, were differentially expressed between endometrial and breast cancer cell lines, but recruitment to target genes was similar in all cell lines. However, XBP1 (X-box-binding protein-1) recruitment and co-recruitment with ERα at target genes was increased with oestradiol treatment in endometrial and not breast cancer cells. XBP1 was also found to be an independent prognostic factor, and high XBP1 expression was associated with significantly improved progression-free survival in endometrial tumours.
Read the full article in Endocrine-Related Cancer 26 31–46