Browsing by Author "Čeleketić, Dušica (24464965300)"

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. © 2007 Springer-Verlag.

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. © 2007 Springer-Verlag.

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 ERβΔ5 isoform 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. © 2006, Institute of Oncology Sremska Kamenica.