Elevated Oestrogen Receptor Splice Variant ERαΔ5 Expression in Tumour-adjacent Hormone-responsive Tissue

Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER) splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT) polymerase chain reaction (PCR) was used to quantitatively assess the levels of four ER splice variants ( ER α Δ 3 , ER α Δ 5 , ER β2 and ER β 5 ), plus the full-length parent isoforms ER α and ER β 1 , in high-risk [tumour-adjacent prostate ( n = 10) or endometrial cancer ( n = 9)] vs . low-risk [benign prostate ( n = 12) or endometrium ( n = 9)], as well as a comparison of UK ( n = 12) vs . Indian ( n = 15) benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ER α Δ 5 . This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ER β 2 in prostate tissue demonstrated that such splice variants are present in comparable, if not greater, amounts as the parent full-length isoform. This small pilot study demonstrates the ubiquitous nature of ER splice variants in these tissue sites and suggests that ER α Δ 5 may be involved in progression of prostate adenocarcinoma.