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Published on: August 2, 2024
Activation of mammalian target of rapamycin in postmenopausal ovarian endometriosis
Abstract:
The purpose of this study was to determine whether Akt and mammalian target of rapamycin (mTOR), downstream targets of phosphatidylinositol 3-kinase, are activated in endometriosis and ovarian cancer specimens. We measured total and phosphorylated levels of Akt and mTOR from 17 frozen ovarian cancers and 15 benign endometriosis specimens (nine from premenopausal women and six from postmenopausal women) by quantitation of signals from western blots using antibodies against these proteins. Elevated phospho-Akt was detected in ovarian cancer versus endometriosis specimens from premenopausal women and endometriosis specimens from postmenopausal women (2.3 +/- 0.45 versus 0.10 +/- 0.06 and 0.17 +/- 0.11; P < 0.05) when the western blot signal of activated kinase was normalized to total kinase levels. Elevated phospho-mTOR was detected in ovarian cancer and postmenopausal endometriosis versus premenopausal endometriosis (0.52 +/- 0.19 and 0.46 +/- 0.29 versus 0.13 +/- 0.08; P < 0.05). Expression of total kinases (normalized to beta-actin) was higher in carcinoma versus endometriosis specimens. Elevation of the active mTOR was specifically detected in postmenopausal endometriosis.
Insights
Akt and mammalian target of rapamycin (mTOR) activation is elevated in ovarian cancer and postmenopausal endometriosis. This suggests potential roles for these signaling pathways in disease development and progression.
Area of Science:
- Oncology
- Gynecology
- Molecular Biology
Background:
- Endometriosis is a chronic, inflammatory condition.
- Ovarian cancer is a leading cause of gynecologic cancer mortality.
- The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is crucial in cell growth and survival.
Purpose of the Study:
- To investigate the activation status of Akt and mTOR in endometriosis and ovarian cancer.
- To compare the levels of activated Akt and mTOR between different patient groups.
Main Methods:
- Western blot analysis was used to quantify total and phosphorylated levels of Akt and mTOR.
- Antibodies specific to Akt and mTOR proteins were employed.
- Signal quantification was normalized to total protein levels and beta-actin.
Main Results:
- Elevated phospho-Akt was observed in ovarian cancer compared to premenopausal endometriosis and in postmenopausal endometriosis.
- Phospho-mTOR levels were higher in ovarian cancer and postmenopausal endometriosis versus premenopausal endometriosis.
- Total kinase expression was higher in ovarian cancer specimens compared to endometriosis.
Conclusions:
- Akt and mTOR signaling pathways are activated in ovarian cancer and endometriosis.
- Specific activation patterns of Akt and mTOR were noted in postmenopausal endometriosis.
- These findings highlight the potential involvement of the PI3K/Akt/mTOR pathway in the pathogenesis of endometriosis and ovarian cancer.
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