The role of estrogen receptors isoforms in breast cancer
Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ER?), as well as the existence of numerous isoforms/splice variants of both ER? and ER?, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ER? isoforms correlates with ER?/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ER? and PR protein levels and for mRNA expression of two ER? isoforms (ER?1 and ER??5). ER? and PR proteins were measured by classical biochemical techniques, and ER? mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ER?1 and ER??5. We found that there is no correlation of ER?1 mRNA expression with ER? and PR protein levels. We confirmed the existence of inverse correlation of ER??5 with PR and of ER??5 with ER? in the group of postmenopausal patients. In the subsets of tumors defined by ER?/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ER? with ER??5 and PR with ER??5isoform suggests that ER??5 may have inhibitory effect on ER? activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ER? and ER? isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance. .