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Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence ( n = 27), including noncancerous benign changes ( n = 15), and the ovarian carcinoma ( n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins' presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.

Idiopathic scoliosis (IS) is a multifactorial disease with epigenetic modifications. Tissue dependent and differentially methylated regions (T-DMRs) may regulate tissue-specific expression of the estrogen receptor 1 gene ( ESR1 ). This study aimed to analyze methylation levels within T-DMR1 and T-DMR2 and its concatenation with ESR1 expression of IS patients. The study involved 87 tissue samples (deep paravertebral muscles, both on the convex and the concave side of the curve, and from back superficial muscles) from 29 girls who underwent an operation due to IS. Patient subgroups were analyzed according to Cobb angle ≤70° vs. >70°. Methylation was significantly higher in the superficial muscles than in deep paravertebral muscles in half of the T-DMR1 CpGs and all T-DMR2 CpGs. The methylation level correlated with ESR1 expression level on the concave, but not convex, side of the curvature in a majority of the T-DMR2 CpGs. The T-DMR2 methylation level in the deep paravertebral muscles on the curvature's concave side was significantly lower in patients with a Cobb angle ≤70° in four CpGs. DNA methylation of the T-DMRs is specific to muscle tissue location and may be related to ESR1 expression regulation. Additionally, the difference in T-DMR2 methylation may be associated with IS severity.

Idiopathic scoliosis (IS) is one of the most common spinal disorders in adolescents. Despite many studies, the etiopathogenesis of IS is still poorly understood. In recent years, the role of epigenetic factors in the etiopathogenesis of IS has been increasingly investigated. It has also been postulated that the development and progression of the disease is related to gender and puberty, and could be associated with estrogen action. Estrogen hormones act via estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). It has been suggested that ESR2 expression is dependent on methylation within its gene promoter. So far, no studies have evaluated local, tissue-specific DNA methylation in patients with IS. Thus, our study aimed to analyze the methylation and expression level of ESR2 in the paraspinal muscles of the convex and concave side of the IS curvature. The methylation level within ESR2 promoter 0N, but not exon 0N, was significantly higher on the concave side of the curvature compared to the convex side. There was no significant correlation between ESR2 expression and methylation level in the promoter 0N on the convexity of thoracic scoliosis, whereas, on the concave side of the curvature, we observed a moderate negative correlation. There was no difference in the methylation levels of the ESR2 promoter and exon 0N between groups of patients with Cobb angle ≤ 70° and > 70° on the concave and convex side of the curvature. We also found no statistically significant correlation between the Cobb angle value and the mean methylation level in either the ESR2 promoter or exon 0N on the convex or concave side of the curvature. Our findings demonstrate that DNA methylation at the ESR2 promoter in deep paravertebral muscle tissue is associated with the occurrence but not with the severity of idiopathic scoliosis.