期刊
CANCER BIOLOGY & THERAPY
卷 7, 期 6, 页码 856-863出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.7.6.5842
关键词
C. elegans transgenics; c-Met receptor tyrosine kinase; juxtamembrane domain mutations; nicotine exposure
类别
资金
- NATIONAL CANCER INSTITUTE [R01CA125541, R01CA100750] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA100750-04, R01 CA125541-02, R01 CA125541, R01 CA100750] Funding Source: Medline
Cancers typically harbour several mutant forms of key cellular genes that contribute to its complex phenotype. Our lab has previously identified gain-of-function mutations in some of the receptor tyrosine kinases such as c-Met in lung cancer. In order to investigate the mutant gene in the context of a whole organism, the current choice of in vivo model is limited to the mouse. To rapidly screen the functional aspects of mutant forms of c-Met detected in lung cancer, we used the nematode C. elegans as the model organism. Transgenic worms were generated that harbour wild type or the frequently seen mutant forms of c-Met in lung cancer (c-MetR988C and c-MetT1010I). Expression of the mutant human c-Met forms in C. elegans consistently resulted in significantly low fecundity and abnormal vulval development characterized by hyperplasia. Interestingly, exposure of c-Met mutant transgenic worms to nicotine resulted in enhanced abnormal vulval development, fecundity and locomotion. Our studies provide first evidence that human c-Met mutations can be studied in C. elegans, and that carcinogens can enhance mutant c-Met function expressed in C. elegans transgenic animals. We therefore propose the use of C. elegans as a model to rapidly assess the role of cancer specific gene mutations in the context of a whole organism.
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