Academic Journal
Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc
| العنوان: | Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc |
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| المؤلفون: | Sharma, Vishva Mitra, Calvo, Jennifer Ann, Draheim, Kyle M., Cunningham, Leslie A., Hermance, Nicole M., Beverly, Levi J., Krishnamoorthy, Veena, Bhasin, Manoj, Capobianco, Anthony J., Kelliher, Michelle A. |
| المساهمون: | Department of Cancer Biology, Jennifer Calvo |
| المصدر: | Molecular and cellular biology ; 26 ; 21 ; 8022-31 |
| سنة النشر: | 2022 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | Amyloid Precursor Protein Secretases, Animals, Apoptosis, Basic Helix-Loop-Helix Transcription Factors, Cell Cycle, Cell Line, Tumor, Enzyme Inhibitors, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Leukemia, T-Cell, Mice, Mutagenesis, Insertional, Oligonucleotide Array Sequence Analysis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-myc, Receptor, Notch1, Retroviridae, Cancer Biology, Life Sciences, Medicine and Health Sciences |
| الوصف: | Recent work with mouse models and human leukemic samples has shown that gain-of-function mutation(s) in Notch1 is a common genetic event in T-cell acute lymphoblastic leukemia (T-ALL). The Notch1 receptor signals through a gamma-secretase-dependent process that releases intracellular Notch1 from the membrane to the nucleus, where it forms part of a transcriptional activator complex. To identify Notch1 target genes in leukemia, we developed mouse T-cell leukemic lines that express intracellular Notch1 in a doxycycline-dependent manner. Using gene expression profiling and chromatin immunoprecipitation, we identified c-myc as a novel, direct, and critical Notch1 target gene in T-cell leukemia. c-myc mRNA levels are increased in primary mouse T-cell tumors that harbor Notch1 mutations, and Notch1 inhibition decreases c-myc mRNA levels and inhibits leukemic cell growth. Retroviral expression of c-myc, like intracellular Notch1, rescues the growth arrest and apoptosis associated with gamma-secretase inhibitor treatment or Notch1 inhibition. Consistent with these findings, retroviral insertional mutagenesis screening of our T-cell leukemia mouse model revealed common insertions in either notch1 or c-myc genes. These studies define the Notch1 molecular signature in mouse T-ALL and importantly provide mechanistic insight as to how Notch1 contributes to human T-ALL. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | Link to Article in PubMed; http://dx.doi.org/10.1128/MCB.01091-06; Mol Cell Biol. 2006 Nov;26(21):8022-31. Epub 2006 Sep 5. doi:10.1128/MCB.01091-06. Link to article on publisher's site; 0270-7306 (Print); http://hdl.handle.net/20.500.14038/32540; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2104&context=gsbs_sp&unstamped=1; https://escholarship.umassmed.edu/gsbs_sp/1105; 680277; gsbs_sp/1105 |
| DOI: | 10.1128/MCB.01091-06 |
| الاتاحة: | https://doi.org/10.1128/MCB.01091-06 https://hdl.handle.net/20.500.14038/32540 https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2104&context=gsbs_sp&unstamped=1 https://escholarship.umassmed.edu/gsbs_sp/1105 |
| Rights: | Copyright © 2006, American Society for Microbiology. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml. |
| رقم الانضمام: | edsbas.19CB73CB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/MCB.01091-06 |
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