Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
C. elegans as a model organism for in vivo screening in cancer: effects of human c-Met in lung cancer affect C. elegans vulva phenotypes
Shahid S. Siddiqui, Sivakumar Loganathan, Soundararajan Krishnaswamy, Leonardo Faoro, Ramasamy Jagadeeswaran and Ravi Salgia
volume 7 | issue 6
June 2008Pages: 856 - 863
Subscribe to this journal for $129/year
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.
Authors
Shahid S. Siddiqui
Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA
Sivakumar Loganathan
Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA.
Soundararajan Krishnaswamy
Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA.
Leonardo Faoro
Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA
Ramasamy Jagadeeswaran
Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA.
Ravi Salgia
Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave MC2115, Chicago, Illinois 60637, USA.