Oncogenic Y68 frame shift mutation of PTEN represents a mechanism of docetaxel resistance in endometrial cancer cell lines
| العنوان: | Oncogenic Y68 frame shift mutation of PTEN represents a mechanism of docetaxel resistance in endometrial cancer cell lines |
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| المؤلفون: | Haiyang Zhang, Michael Xie, Nicholas A. Cacalano, Song Wang, Qiuju Liu, Mitchell Kamrava, Gottfried E. Konecny, Shunzi Jin, He Zhu |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific reports, vol 9, iss 1 Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Drug Resistance, lcsh:Medicine, Apoptosis, Docetaxel, Gene mutation, medicine.disease_cause, 0302 clinical medicine, Tumor Cells, Cultured, 2.1 Biological and endogenous factors, Aetiology, Frameshift Mutation, lcsh:Science, Cancer, Mutation, Multidisciplinary, Cultured, Tumor, biology, Cell Cycle, Cell cycle, Tumor Cells, Gene Expression Regulation, Neoplastic, Lipid phosphatase activity, Female, KRAS, Biotechnology, Antineoplastic Agents, Article, 03 medical and health sciences, Rare Diseases, Uterine Cancer, medicine, Biomarkers, Tumor, Genetics, PTEN, Humans, Cell Proliferation, Neoplastic, Endometrial cancer, lcsh:R, PTEN Phosphohydrolase, medicine.disease, Endometrial Neoplasms, 030104 developmental biology, Gene Expression Regulation, Drug Resistance, Neoplasm, Gamma Rays, biology.protein, Cancer research, Neoplasm, lcsh:Q, 030217 neurology & neurosurgery, Biomarkers |
| الوصف: | In this study, we aimed to identify mutations of key genes associated with docetaxel resistance in nine endometrial cancer cell lines. Endometrial cancers are associated with several critical gene mutations, including PIK3A, PTEN, and KRAS. Different gene mutations in endometrial cancer cells have varied responses to anticancer drugs and cancer therapies. The most frequently altered gene in endometrioid endometrial carcinoma tumors is PTEN. PTEN protein has lipid phosphatase and protein phosphatase activity, as well as other functions in the nucleus. Although the tumor-suppressive function of PTEN has mainly been attributed to its lipid phosphatase activity, a role for PTEN protein phosphatase activity in cell cycle regulation has also been suggested. Various tumor type-specific PTEN mutations are well documented. Here, nine endometrioid endometrial cancer cell lines with PIK3A, PTEN, and KRAS gene mutations were treated with docetaxel and radiation. One mutation with a docetaxel drug-resistant effect was a truncated form of PTEN. Among PTEN mutations in endometrial cancer cells, the Y68 frame shift mutation of PTEN constitutes a major mechanism of resistance to docetaxel treatment. The molecular mechanism involves truncation of the 403 amino acid PTEN protein at amino acid 68 by the Y68 frame shift, leading to the loss of PTEN protein phosphatase and lipid phosphatase activities. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26b045271579b47576d9c352272d1731 http://link.springer.com/article/10.1038/s41598-019-38585-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....26b045271579b47576d9c352272d1731 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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