Be stimulated by E2 [21]. ER- interacts with RUNX2 through multiple domains
Be stimulated by E2 [21]. ER- interacts with RUNX2 through multiple domains and the repression occurs independently of the activation of estrogen response element containing genes. RUNX2 suppresses estrogen activity by decreasing the effect of estradiol on reporter gene expression driven by the estrogen receptor response element [10]. Recent studies on breast cancer cells disclosed that ER- physically binds RUNX2 and inhibits expression of several RUNX2 target genes, providing a strong antagonistic correlation between the two genes in a different cellular type [22,23]. This opposing effect is verified by our PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27766426 results. The non-parametric correlation between RUNX2 and E2 is statistically significant and indicates negative association (r = -0.40, p = 0.010).Papamentzelopoulou et al. Reproductive Biology and Endocrinology 2012, 10:99 http://www.rbej.com/content/10/1/Page 7 ofComparing E2 levels between women with and without RUNX2 expression, women without expression present higher levels to a statistically significant degree (2957 pg/ml versus 1874 pg/ml, p = 0.013). An explanation of higher E2 levels in the group without RUNX2 expression in our study could be the down egulation phenomenon in RUNX2 expression that may occur in this group of patients. Since E2-bound ER- suppresses RUNX2 in a strong and specific Chloroquine (diphosphate) custom synthesis mechanism, additional changes in ER- expression between groups, apart from the different E2 levels, could also possibly affect RUNX2 expression, although ER- has not been investigated in our study.7.8.9. 10. 11.12.13.Conclusions In summary, even though RUNX2 remains a less studied protein for its association with controlled ovarian stimulation outcome in ART treatment, a possible correlation of RUNX2 gene expression in cumulus cells and ovarian stimulation factors is observed in our study. It is remarkable that the detectable gene expression is not associated with a favorable outcome. The possible interaction of this transcription factor with different pathways involved in ovulation and implantation needs further investigation to confirm its inhibitory effect.Competing interests The authors declare PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28549975 that they have no competing interests. Authors’ contributions MP analyzed RUNX2 expression by real-time PCR and wrote first draft. DM set up real-time PCR, supervised MP. VD and HT collected cumulus cells. RB collected cumulus cells and cultured embryos. SM performed the statistical analysis. FM and EA completed writing of paper. KK gained approvals, performed U/S scans and retrieved oocytes. DL led research programme, supervised researchers and completed writing of paper. All authors read and approved the final manuscript. Received: 28 June 2012 Accepted: 24 November 2012 Published: 28 November 2012 References 1. Devroey P, Fauser BCJM, Diedrich K: Approaches to improve the diagnosis and management of infertility. Hum Reprod Update 2009, 15(4):391?08. 2. Stock M, Schafer H, Fliegauf M, Otto F: Identification of novel target genes of the bone-specific transcription factor RUNX2. J Bone Miner Res 2004, 19:959?72. 3. Wang GX, Sun RP, Song FL: A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia. Genet Mol Res 2010, 9(1):41?7. 4. Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, Wijnen AJ, Jones SN, et al: A RUNX2 threshold for the cleidocranial dysplasia phenotype. Hum Mol Genet 2009, 18(3):556?68. 5. Hernandez-Gonzalez I, Gonzalez-Robayna I, Shimada M, Wayne CM, Ochsner SA, White L, Richards.
