Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice

View/ Open
Author
Bajwa, Preety
Nielsen, Sarah
Lombard, Janine M.
Rassam, Loui
Nahar, Pravin
Wilkinson, J. Erby
Miller, Richard A.
Tanwar, Pradeep S
Published Version
https://doi.org/10.18632/oncotarget.13919Metadata
Show full item recordCitation
Bajwa, Preety, Sarah Nielsen, Janine M. Lombard, Loui Rassam, Pravin Nahar, Bo R. Rueda, J. Erby Wilkinson, Richard A. Miller, and Pradeep S Tanwar. 2017. “Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice.” Oncotarget 8 (5): 7265-7275. doi:10.18632/oncotarget.13919. http://dx.doi.org/10.18632/oncotarget.13919.Abstract
During aging, uncontrolled epithelial cell proliferation in the uterus results in endometrial hyperplasia and/or cancer development. The mTOR signaling pathway is one of the major regulators of aging as suppression of this pathway prolongs lifespan in model organisms. Genetic alterations in this pathway via mutations and/or amplifications are often encountered in endometrial cancers. However, the exact contribution of mTOR signaling and uterine aging to endometrial pathologies is currently unclear. This study examined the role of mTOR signaling in uterine aging and its implications in the development of endometrial hyperplasia. The hyperplastic endometrium of both postmenopausal women and aged mice exhibited elevated mTOR activity as seen with increased expression of the pS6 protein. Analysis of uteri from Pten heterozygous and Pten overexpressing mice further confirmed that over-activation of mTOR signaling leads to endometrial hyperplasia. Pharmacological inhibition of mTOR signaling using rapamycin treatment suppressed endometrial hyperplasia in aged mice. Furthermore, treatment with mTOR inhibitors reduced colony size and proliferation of a PTEN negative endometrial cancer cell line in 3D culture. Collectively, this study suggests that hyperactivation of the mTOR pathway is involved in the development of endometrial hyperplasia in aged women and mice.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352319/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630469
Collections
- HMS Scholarly Articles [17714]
Contact administrator regarding this item (to report mistakes or request changes)