دورية أكاديمية
Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice.
| العنوان: | Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice. |
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| المؤلفون: | Felix, K., Polack, A., Pretsch, W., Jackson, S.H., Feigenbaum, L., Bornkamm, G.W., Janz, S. |
| المصدر: | Cancer Res. 64, 530-537 (2004) |
| بيانات النشر: | AACR |
| سنة النشر: | 2004 |
| المجموعة: | PuSH - Publikationsserver des Helmholtz Zentrums München |
| مصطلحات موضوعية: | STRAND BREAK REPAIR, IN-VIVO MUTATIONS, ELEVATED MUTANT FREQUENCIES, UNCOUPLES DNA-REPLICATION, C-MYC, REACTIVE OXYGEN, TRANSCRIPTIONAL ACTIVATION, INDUCED LYMPHOMAGENESIS, MOUSE PLASMACYTOMAS, MULTIPLE MUTATIONS |
| الوصف: | Mutator phenotypes, a common and largely unexplained attribute of human cancer, might be better understood in mouse tumors containing reporter genes for accurate mutation enumeration and analysis. Previous work on peritoneal plasmacytomas (PCTs) in mice suggested that PCTs have a mutator phenotype caused by Myc-deregulating chromosomal translocations and/or phagocyte-induced mutagenesis due to chronic inflammation. To investigate this hypothesis, we generated PCTs that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the assessment of mutations in vivo. PCTs exhibited a 5.5 times higher mutant frequency in lacZ (40.3 +/- 5.1 x 10(-5)) than in normal B cells (7.36 +/- 0.77 x 10(-5)), demonstrating that the tumors exhibit the phenotype of increased mutability. Studies on lacZ mutant frequency in serially transplanted PCTs and phagocyte-induced lacZ mutations in B cells in vitro indicated that mutant levels in tumors are not determined by exogenous damage inflicted by inflammatory cells. In vitro studies with a newly developed transgenic model of inducible Myc expression (Tet-off/MYC) showed that deregulated Myc sensitizes B cells to chemically induced mutations, but does not cause, on its own, mutations in lacZ. These findings suggested that the hypermutability of PCT is governed mainly by intrinsic features of tumor cells, not by deregulated Myc or chronic inflammation. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0008-5472 1538-7445 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/undefined; info:eu-repo/semantics/altIdentifier/isbn/0008-5472; info:eu-repo/semantics/altIdentifier/pissn/0008-5472; info:eu-repo/semantics/altI; https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=1757Test; urn:isbn:0008-5472; urn:issn:0008-5472; urn:issn:1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-03-2602 |
| الإتاحة: | https://doi.org/10.1158/0008-5472.CAN-03-2602Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=1757Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.28F0364F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00085472 15387445 |
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| DOI: | 10.1158/0008-5472.CAN-03-2602 |