التفاصيل البيبلوغرافية
| العنوان: |
Targeted mutations in the ATR pathway define agent-specific requirements for cancer cell growth and survival |
| المؤلفون: |
Ivan Pradilla, Deborah Wilsker, Fred Bunz, Thomas Helleday, Jon Chung, Eva Petermann |
| سنة النشر: |
2011 |
| مصطلحات موضوعية: |
Cancer Research, Cell Survival, Upstream and downstream (transduction), Antineoplastic Agents, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Biology, Protein Serine-Threonine Kinases, Article, Cell Line, Tumor, Humans, CHEK1, Cell Proliferation, Cell growth, Cyclin-dependent kinase 2, Cyclin-Dependent Kinase 2, DNA replication, Cell biology, Oncology, Cancer cell, Checkpoint Kinase 1, Colonic Neoplasms, biology.protein, Signal transduction, biological phenomena, cell phenomena, and immunity, Protein Kinases, Signal Transduction |
| الوصف: |
Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase–specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a subset of the drugs tested. These results show that specifically inhibiting the Cdk2/ATR/Chk1 pathway via distinct regulators can differentially sensitize cancer cells to a wide range of therapeutic agents. Mol Cancer Ther; 11(1); 98–107. ©2011 AACR. |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d52165534d378a658df1544877d58487
https://europepmc.org/articles/PMC3256256/ |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....d52165534d378a658df1544877d58487 |
| قاعدة البيانات: |
OpenAIRE |
