The role of estrogen receptors isoforms in breast cancer

Abstract

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 (ERβ), as well as the existence of numerous isoforms/splice variants of both ERα and ERβ, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ERβ isoforms correlates with ERα/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ERα and PR protein levels and for mRNA expression of two ERβ isoforms (ERβ1 and ERβΔ5). ERα and PR proteins were measured by classical biochemical techniques, and ERβ mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ERβ1 and ERβΔ5. We found that there is no correlation of ERβ1 mRNA expression with ERα and PR protein levels. We confirmed the existence of inverse correlation of ERβΔ5 with PR and of ERβΔ5 with ERα in the group of postmenopausal patients. In the subsets of tumors defined by ERα/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 ERα with ERβΔ5 and PR with ERβΔ5isoform suggests that ERβΔ5 may have inhibitory effect on ERα activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ERα and ERβ isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance.