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Research Paper

Suppressive Effect of Modified Dominant Negative RAS Mutant on Human Cancer by Gene Transfer with Non-Viral Vector

H Suzuki, S Kuzumaki, K Nakagawa, M Takimoto and T Shichinohe

volume 5 | issue 11

November 2006
Pages: 1487 - 1491

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N116Y, H-RAS mutant, has dominant negative activity in the RAS function and a suppressive effect on the growth of various types of cancer cells. However, a replication error of N116Y is of potential concern for carcinogenesis in clinical application. To decease the concern, we constructed modified N116Y by deleting the carboxyl terminus, which is necessary for the oncogenic function of Ras. One of the C-terminal deletion mutants of N116Y, N116Y-Cdel2 showed a growth-suppressing effect on various human cancer cell lines in vitro: the cervical cancer cell line HeLa, the pancreatic cancer cell line PCI43, the colon cancer cell lines SW480 and LoVo, and the tongue cancer cell line SAS. In addition, the suppressive effect of N116Y-Cdel2 on LoVo cells was also observed in vivo using a non-viral gene transfer vector, HVJ envelope. Our experiments suggest that the modified N116Y is a potential candidate gene for human cancer gene therapy.

Authors

H Suzuki

Osaka University, Osaka, Japan

S Kuzumaki

Hokkaido University, Hokkaido, Japan

K Nakagawa

Hokkaido University, Hokkaido, Japan

M Takimoto

Hokkaido University, Hokkaido, Japan

T Shichinohe

Hokkaido University, Hokkaido, Japan




We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.