Abstract
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.
Highlights
Ovarian cancer is one of the deadliest malignant tumors affecting woman
Taking into consideration the role of estrogen-related signaling pathways, in our study we investigated whether the ESR1, ESR2, PELP1, and SRC mRNA expression levels, as well as the generated expression ratios, are associated with ovarian tumor manifestation
For the tissues obtained from patients with benign ovarian changes vs. ovarian cancer patients, the former was significantly younger (Me = 51y vs. 63y; multiple comparison p-value p = 0.0357)
Summary
Ovarian cancer is one of the deadliest malignant tumors affecting woman. The overall incidence of epithelial ovarian cancers varies from 9 to 17 per 100,000 and is highest in high-income countries. Epithelial ovarian cancers mostly occur after the age of 50 years, and this incidence rate increases proportionately with age [1]. Studies showed that DNA damage response is a crucial hallmark of high-grade epithelial ovarian tumors, leading to a specific interest in BRCA genes. Both BRCA1 and BRCA2 genes remain two key tumor suppressors involved in the double-strand breaks DNA repair pathway through the homologous recombination. From a translational point of view, a clinical issue related to therapy success is identifying reliable ovarian cancer biomarkers [2]
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