جهت دسترسی به کاربرگه ی زیر، از این لینک استفاده کنید. http://dl.kums.ac.ir/handle/Hannan/82155
Title: Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Keywords: cancer biology;Cell Biology;Oncology;cancer: lung
Publisher: Public Library of Science
Description: Background: Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the EGFR inhibitors erlotinib and gefitinib, but the transforming potential of specific mutations and their relationship to drug sensitivity have not been described. Methods and Findings: Here, we demonstrate that EGFR active site mutants are oncogenic. Mutant EGFR can transform both fibroblasts and lung epithelial cells in the absence of exogenous epidermal growth factor, as evidenced by anchorage-independent growth, focus formation, and tumor formation in immunocompromised mice. Transformation is associated with constitutive autophosphorylation of EGFR, Shc phosphorylation, and STAT pathway activation. Whereas transformation by most EGFR mutants confers on cells sensitivity to erlotinib and gefitinib, transformation by an exon 20 insertion makes cells resistant to these inhibitors but more sensitive to the irreversible inhibitor CL-387,785. Conclusion: Oncogenic transformation of cells by different EGFR mutants causes differential sensitivity to gefitinib and erlotinib. Treatment of lung cancers harboring EGFR exon 20 insertions may therefore require the development of alternative kinase inhibition strategies.
URI: http://dl.kums.ac.ir/handle/Hannan/82155
Standard no: Greulich, Heidi, Tzu-Hsiu Chen, Whei Feng, Pasi A. Jänne, James V. Alvarez, Mauro Zappaterra, Sara E. Bulmer, et al. 2005. Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants. PLoS Medicine 2(11): e313.
1549-1277
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878949
Appears in Collections:Harvard Medical School

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