A Transgenic Mouse Model for Understanding Rev1 and Lung Cancer

  • Wang, Zhigang (PI)

Grants and Contracts Details


Our long-term objectives are to understand the role ofRevl in lung cancer development and to develop a novel strategy for cancer prevention by inhibiting the Revl function. Cancer is a highly complex disease involving many genetic alterations. Mutagenesis can lead to gene malfunction, thus it constitutes a key factor to carcinogenesis. Without mutation, most, if not all, cancers would not be able to form. DNA damage is a major source of mutagenesis. The ability of most carcinogens to induce cancer is attributable to their ability to damage DNA and subsequently cause mutations. In eukaryotes, the Pol zeta pathway is a major mechanism of damage-induced mutagenesis. This mutagenesis pathway requires the function of Pol zeta (the Rev3-Rev7 complex) and Rev!. The human REVl gene was cloned in our laboratory. Others and we have demonstrated that Revl is critical for DNA damage-induced mutagenesis in yeast. Accumulating evidence indicates that Revl also plays a key role in DNA damage-induced mutagenesis in higher eukaryotes. Therefore, we hypothesize that Revl plays a key role in lung carcinogenesis, and that inhibiting Revl may lead to cancer prevention. To definitively test our hypotheses, we propose to establish a transgenic mouse model in which the Rev 1 function is inactivated by deleting the mouse Revl gene through gene knockout technology. Our specific aims are (1) to generate Revl conditional knockout mice; and (2) to test our hypothesis that mice deficient in Revl are deficient in DNA damage-induced mutagenesis. These studies should yield critical data for a major NIH ROl grant application. An NIH ROl grant will make it possible for us to achieve our long-term objectives of understanding the role ofRevl in lung cancer development and developing a novel strategy for cancer prevention by inhibiting the Rev 1 function. University of Kentucky 11/22/06
Effective start/end date9/1/078/31/10


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.