The present study was designed to evaluate the E2-independent effect of ERα/β on leptin-mediated cell invasion and cell proliferation in ovarian cancer.
Estrogen receptor (ER) positivity and progesterone receptor (PR) positivity were significant protective factors against subsequent BC and ovarian cancer.
Ovarian cancer is a major gynaecological cancer with different subtypes and studies have suggested that estrogen receptor (ER) or progesterone receptor (PR) positivity are associated with better clinical outcomes.
This study uses primary cultures of mouse ovarian surface epithelium (OSE) to demonstrate that one possible mechanism by which estrogen accelerates the initiation of ovarian cancer is by up-regulation of microRNA-378 via the ESR1 pathway to result in the down-regulation of a tumour suppressor called Disabled-2 (Dab2).
We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC.
Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08-0.42, <i>p</i> = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10-0.53, <i>p</i> = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease.
Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer.
Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women.
In the present study, estrogen receptor α (ERα)-negative/GPER-positive OVCAR5 ovarian cancer cell line was used to investigate the role of GPER in the migration and invasion of ovarian cancer.
Despite estrogen receptor (ER) expression in 67% of OVCAs, small anti-estrogen therapy trials have been disappointing and the benefit of hormonal therapy has not been systematically studied in large well-designed trials.
There was significant enrichment of ESR1 binding present in multiple datasets near genomic regions associated with breast cancer (7.45-fold, p = 0.001), height (2.45-fold, p = 0.002), multiple sclerosis (5.97-fold, p < 0.0002) and prostate cancer (4.47-fold, p = 0.0008), and suggestive evidence of ESR1 enrichment for regions associated with coronary artery disease, ovarian cancer, Parkinson's disease, polycystic ovarian syndrome and testicular cancer.
Meanwhile, the at-risk A allele was positively related with the occurrence of mucinous ovarian cancer (OR = 3.48; 95% CI:1.15-6.83; P = 0.001), low degree of differentiation (OR = 1.87; 95% CI:1.03-3.47; P = 0.003), lymph node metastasis (OR = 1.69; 95% CI: 1.14-2.75; P = 0.010) and estrogen receptor positive (OR = 2.72; 95% CI: 1.38-4.81; P = 0.002).
A SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope 1 (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis.
To study a potential role of estrogen receptor-alpha gene amplification for estrogen receptor overexpression in ovarian cancer, a tumor tissue microarray containing 428 ovarian cancers was analyzed by fluorescence in situ hybridization for estrogen receptor-alpha gene amplification and immunohistochemistry for estrogen receptor expression.