Mammalian Target of Rapamycin Complex 1 and Cyclooxygenase 2 Pathways Cooperatively Exacerbate Endometrial Cancer
| Autor: | Lora Hedrick Ellenson, Jumpei Terakawa, Mikihiro Yoshie, Sudhansu K. Dey, Mir Ezharul Hossain, Monica Cappelletti, Takiko Daikoku, Peiying Yang |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cell Survival
Phosphatase Blotting Western Apoptosis mTORC1 macromolecular substances Mechanistic Target of Rapamycin Complex 1 Pathology and Forensic Medicine Mice Cell Line Tumor medicine Tensin Animals Humans Mice Knockout Sirolimus Sulfonamides Antibiotics Antineoplastic biology Cyclooxygenase 2 Inhibitors Reverse Transcriptase Polymerase Chain Reaction TOR Serine-Threonine Kinases Carcinoma Cancer food and beverages Regular Article medicine.disease Immunohistochemistry 3. Good health Endometrial Neoplasms Disease Models Animal Celecoxib Cyclooxygenase 2 Multiprotein Complexes biology.protein Cancer research Pyrazoles Female Cyclooxygenase Signal transduction biological phenomena cell phenomena and immunity medicine.drug Signal Transduction |
| Zdroj: | The American Journal of Pathology. (9):2390-2402 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2014.05.023 |
| Popis: | The underlying causes of endometrial cancer (EMC) are poorly understood, and treatment options for patients with advanced stages of the disease are limited. Mutations in the phosphatase and tensin homologue gene are frequently detected in EMC. Cyclooxygenase 2 (Cox2) and mammalian target of rapamycin complex 1 (mTORC1) are known downstream targets of the phosphatase and tensin homologue protein, and their activities are up-regulated in EMC. However, it is not clear whether Cox2 and mTORC1 are crucial players in cancer progression or whether they work in parallel or cooperatively. In this study, we used a Cox2 inhibitor, celecoxib, and an mTORC1 inhibitor, rapamycin, in mouse models of EMC and in human EMC cell lines to explore the interactive roles of Cox2 and mTORC1 signaling. We found that a combined treatment with celecoxib and rapamycin markedly reduces EMC progression. We also observed that rapamycin reduces Cox2 expression, whereas celecoxib reduces mTORC1 activity. These results suggest that Cox2 and mTORC1 signaling is cross-regulated and cooperatively exacerbate EMC. |
| Databáze: | OpenAIRE |
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