Evaluation of ovarian cancer risk in granulosa cells treated with steroid-depleted endometriosis serum: Role of NF-κB/RelA and AKT

Asghari S, Samira Asghari, Amir Valizadeh Dizajeykan, Amir Valizadeh, Valizadeh Dizajeykan A, Majid Ahmadi, Abolfazl Barzegari, Reza Rikhtegar, Rikhtegar R, Sanam Dolati, Shahla Danaii, Abdollahi-Fard S, Sedigheh Abdollahi-Fard, Sedigheh Abdollahi‐Fard, Nouri M, Mohammad Nouri, Mahdi Mahdipour, Mehdi Yousefi
Journal of cellular physiology · 2018 · vol. 234(7) , pp. 12011–12018 · doi:10.1002/jcp.27862 · PMID:30515820 · W2902307854
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Steroid-depleted serum from endometriosis patients significantly increased AKT and NF-κB/RelA expression while decreasing apoptosis in granulosa cells, suggesting a potential risk for granulosa cell tumor development.

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Abstract

BACKGROUND: Despite at the beginning known as a benign disease, endometriosis is defined as a risk factor for developing ovarian carcinoma. The effect of endometriosis on ovarian malignancy is known but its role in granulosa cell tumor is still unclear. METHODS AND MATERIALS: In this study, serum samples were collected from patients with endometriosis and divided into whole and steroid-depleted groups. Desertification was performed according to the charcoal-dextran protocol and sera were added to the culture media of granulosa cells retrieved from tubal or male factor infertile women. Quantitative real-time polymerase chain reaction and flow cytometry were performed to determine the expression level of inflammatory and apoptotic genes and apoptosis level of granulosa cells. The total concentration of lipid was measured using gas chromatography method in the granulosa cells. RESULTS: Results revealed that the expression of AKT and NF-κB/RelA gene was significantly higher in the granulosa cells treated with steroid-depleted serum obtained from patients with distrificated endometriosis (DE) compared with the control group (9.39- and 7.9-folds, respectively; p < 0.0001). In the DE group, the declined pattern of expression was observed for the genes related to apoptosis. The synthesis of saturated fatty acids was significantly decreased; however, unsaturated fatty acids showed increased levels in the DE group. CONCLUSION: The effect of steroids on endometriosis is contradictory. The level of cortisol and sex hormones could be affected by endometriosis, causing alterations of the disease progression. Reduced level of steroid hormones in patients with endometriosis may be considered as a critical risk factor for granulosa cell tumor.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Granulosa Cells NF-kappa B Proto-Oncogene Proteins c-akt Adult Adult Carcinoma, Ovarian Epithelial Carcinoma, Ovarian Epithelial Carcinoma, Ovarian Epithelial Endometriosis Endometriosis Female Female Granulosa Cells Granulosa Cells Humans Humans Infertility, Female Infertility, Female Infertility, Female

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