Expression of estrogen receptor β wt isoform (ERβ1) and ERβΔ5 splice variant mRNAs in sporadic breast cancer

In addition to Estrogen Receptor α (ERα) and Progesterone Receptor (PR), the Second Estrogen Receptor (ERβ) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. In this study, the expression of ERβ1 mRNA (wild type of β receptor) and splice variant ERβΔ5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ERα and PR protein levels and with clinical and histopathological parameters. We found the inverse correlation of ERβΔ5 mRNA expression with the levels of PR and ERα proteins in the group of postmenopausal patients; we also report the lower expression of ERβ1 and ERβΔ5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (≤20 mm, T1). The decrease of ERβΔ5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. As far as we know, this is the first study in which ERβΔ5 mRNA splice variant was quantified by real-time RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ERβ1, ERβ2, and ERβ5 isoforms. The higher expression of ERβΔ5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ERβΔ5 mRNA decreases in estrogen-dependent breast cancer.