دورية أكاديمية
أعرض في EDS

Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis.

التفاصيل البيبلوغرافية
العنوان: Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis.
المؤلفون: To MD; Thoracic Oncology Program, Department of Surgery, University of California San Francisco, San Francisco, CA 94115, USA., Rosario RD, Westcott PM, Banta KL, Balmain A
المصدر: Oncogene [Oncogene] 2013 Aug 22; Vol. 32 (34), pp. 4028-33. Date of Electronic Publication: 2012 Sep 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
مواضيع طبية MeSH: Epistasis, Genetic* , Mutation*, Cell Transformation, Neoplastic/*genetics , Genes, ras/*genetics , Lung/*metabolism , Skin/*metabolism, 9,10-Dimethyl-1,2-benzanthracene ; Animals ; Cell Transformation, Neoplastic/metabolism ; Female ; Lung/pathology ; Lung Neoplasms/chemically induced ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Male ; Mice ; Mice, Knockout ; Models, Genetic ; Skin/pathology ; Skin Neoplasms/chemically induced ; Skin Neoplasms/genetics ; Skin Neoplasms/metabolism ; Urethane ; ras Proteins/genetics ; ras Proteins/metabolism
مستخلص: Ras oncogenes (Hras, Kras and Nras) are important drivers of carcinogenesis. However, tumors with Ras mutations often show loss of the corresponding wild-type (WT) allele, suggesting that proto-oncogenic forms of Ras can function as a suppressor of carcinogenesis. In vitro studies also suggest that WT Ras proteins can suppress the tumorigenic properties of alternate mutant Ras family members, but in vivo evidence for these heterologous interactions is lacking. We have investigated the genetic interactions between different combinations of mutant and WT Ras alleles in vivo using carcinogen-induced lung and skin carcinogenesis in mice with targeted deletion of different Ras family members. The major suppressor effect of WT Kras is observed only in mutant Kras-driven lung carcinogenesis, where loss of one Kras allele led to increased tumor number and size. Deletion of one Hras allele dramatically reduced the number of skin papillomas with Hras mutations, consistent with Hras as the major target of mutation in these tumors. However, skin carcinoma numbers were very similar, suggesting that WT Hras functions as a suppressor of progression from papillomas to invasive squamous carcinomas. In the skin, the Kras proto-oncogene functions cooperatively with mutant Hras to promote papilloma development, although the effect is relatively small. In contrast, the Hras proto-oncogene attenuated the activity of mutant Kras in lung carcinogenesis. Interestingly, loss of Nras increased the number of mutant Kras-induced lung tumors, but decreased the number of mutant Hras-induced skin papillomas. These results show that the strongest suppressor effects of WT Ras are only seen in the context of mutation of the cognate Ras protein, and only relatively weak effects are detected on tumor development induced by mutations in alternative family members. The data also underscore the complex and context-dependent nature of interactions between proto-oncogenic and oncogenic forms of different Ras family members during tumor development.
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معلومات مُعتمدة: R01 CA111834 United States CA NCI NIH HHS; CA111834-01 United States CA NCI NIH HHS; CA84244 United States CA NCI NIH HHS; U01 CA084244 United States CA NCI NIH HHS; T32 GM007175 United States GM NIGMS NIH HHS
المشرفين على المادة: 3IN71E75Z5 (Urethane)
57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
EC 3.6.5.2 (ras Proteins)
تواريخ الأحداث: Date Created: 20120905 Date Completed: 20131126 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3515692
DOI: 10.1038/onc.2012.404
PMID: 22945650
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5594
DOI:10.1038/onc.2012.404