Abstract PS16-18: Inhibition of mTOR signaling by rapamycin abrogates mammary stem/progenitor cell activity in aged mice
| Autor: | James F. Nelson, Lu-Zhe Sun, Larry E. Broome, Hakim Bouamar |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Cancer Research. 81:PS16-18 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.sabcs20-ps16-18 |
| Popis: | Previous studies have shown an altered physiology in the mammary gland of aged mice, with mammary ducts displaying increased tertiary branching along with an enriched myoepithelial population compared to younger mice. It is the population of myoepithelial cells residing in the basal layer of mammary ducts that is thought to be responsible for the development of the mammary gland. These qualities have been attributed to the mammary stem cells (MaSCs) that reside in this population and are capable of regenerating the mammary gland when implanted in an empty mammary fat pad, indicating their bipotent nature. It is not known however, if these stem cells are responsible for the aging mammary gland phenotype and the increased risk of cancer seen in aging mammals. Our preliminary studies showed that rapamycin could be utilized as a MaSC inhibitor and clinical trials are currently under way investigating the role of rapamycin in inhibiting MaSC function and abrogating biomarkers associated with invasive BC progression. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates growth, proliferation, and survival in cells and is often upregulated in cancer. Rapamycin is an extremely selective inhibitor of mTORC1 function and its downstream signaling. In this study, aged mice fed ad lib with microencapsulated rapamycin showed decreased mTOR activity in the mammary ducts as shown by immunohistochemistry in aged mice. Treated mouse breast tissue also displayed a decreased population of Lin- CD24low CD49fhi myoepithelial/basal cells along with decreased tertiary branching in the ductal morphology, effectively reversing the aged mammary gland phenotypes. MaSC inhibition by rapamycin was also shown using sphere formation efficiency (SFE) assays after sorting the luminal (Lin- CD24hi CD49flow) and basal (Lin- CD24low CD49fhi) epithelial cells using Florescence Activated Cells Sorting (FACS) in a free suspension culture. Together, these findings show a possible use in regulating MaSCs by rapamycin and its potential in preventing age-related diseases such as breast cancer. Citation Format: Larry E. Broome, Hakim Bouamar, James F. Nelson, Lu-Zhe Sun. Inhibition of mTOR signaling by rapamycin abrogates mammary stem/progenitor cell activity in aged mice [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-18. |
| Databáze: | OpenAIRE |
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