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The mammalian target of rapamycin protein expression in human granulosa cell tumors
Onur Güralp1, Tugan Bese2, Gamze Bildik3
1Department of Obstetrics and Gynecology, Carl von Ossietszky Oldenburg University, Klinikum AöR, Oldenburg, Germany
Objective:
To investigate the role of mammalian target of rapamycin (mTOR) in human granulosa cell ovarian tumors and the therapeutic effect of rapamycin in COV434 mitotic granulosa cell lines.
Material And Methods:
A retrospective evaluation of the medical records and pathologic sections of patients with granulosa cell ovarian carcinoma was performed. mTOR and p-mTOR expression was immunohistochemically investigated. A COV434 cell culture were treated with 0.5, 1, 2, and 5 μM rapamycin. Real-time growth curve analysis via xCELLigence system and apoptotic cell analysis via YO-PRO™-1 Iodide were performed to assess the therapeutic effect of rapamycin on cancer cells.
Results:
A total of twenty patients were evaluated. mTOR staining was detected in 18 (90%) patients. Mild, moderate, intense, and very intense staining was observed in three (15%), eight (40%), six (30%), and one (5%) sample, respectively. The mean mTOR staining ratio was 59±41%. P-mTOR staining was observed in two (10%) patients. One (5%) patient had 5% staining, and one (5%) patient had 100% staining for p-mTOR. Both of the latter patients had very intense staining. Rapamycin caused a dose-dependent growth arrest and induced apoptosis in COV434 mitotic granulosa cells. The real-time growth curves of the cells treated with these drugs were distinguished by a marked reduced slope after exposure for several hours, indicating a rapid onset of apoptosis. Live/dead cell analysis with YO-PRO-1 staining showed that rapamycin induced apoptosis in 24% of the cells when used at 1 μM concentration, whereas the rate increased to 61% and 72% when the cells were treated with 2 μM and 5 μM rapamycin, respectively.
Conclusion:
mTOR expression is observed in various degrees in 90%, and p-mTOR expression is observed in only 10% of patients with granulosa cell ovarian carcinoma. Rapamycin caused a dose-dependent growth arrest and apoptosis in COV434 mitotic granulosa cells.
Insights
Mammalian target of rapamycin (mTOR) is highly expressed in granulosa cell ovarian tumors. Rapamycin effectively inhibits tumor cell growth and induces apoptosis in these cells, showing therapeutic potential.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Mammalian target of rapamycin (mTOR) signaling plays a crucial role in various cellular processes, including cell growth and proliferation.
- Dysregulation of mTOR is implicated in the pathogenesis of several cancers, including ovarian tumors.
Purpose of the Study:
- To investigate the expression of mTOR in human granulosa cell ovarian tumors.
- To evaluate the therapeutic efficacy of rapamycin in inhibiting the proliferation and inducing apoptosis of COV434 granulosa cell lines.
Main Methods:
- Retrospective analysis of medical records and immunohistochemical assessment of mTOR and phosphorylated mTOR (p-mTOR) expression in 20 patients with granulosa cell ovarian carcinoma.
- Treatment of COV434 cell lines with varying concentrations of rapamycin (0.5, 1, 2, and 5 μM).
- Real-time cell growth analysis using the xCELLigence system and apoptosis assessment via YO-PRO™-1 Iodide staining.
Main Results:
- mTOR expression was detected in 90% of the evaluated granulosa cell ovarian carcinoma samples, with varying staining intensities.
- p-mTOR expression was observed in 10% of the patients.
- Rapamycin demonstrated a dose-dependent inhibition of COV434 cell proliferation and induced significant apoptosis, with higher concentrations leading to increased cell death.
Conclusions:
- mTOR is frequently expressed in granulosa cell ovarian carcinoma, suggesting its involvement in tumor development.
- Rapamycin exhibits potent anti-proliferative and pro-apoptotic effects on COV434 cells, highlighting its potential as a therapeutic agent for this type of ovarian cancer.
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