A Bioinformatics-Based Strategy Identifies c-Myc and Cdc25A as Candidates for the Apmt Mammary Tumor Latency Modifiers

December 9, 2003

Institute of Bioinformatics

陳孟均Chen Meng Chung

Abstract

The PyVT transgenic animals induce mammary tumor, but the two epistatically interacting modifier loci, Apmt1 and Apmt2 acceleration the PyVT –induced the mammary tumor. To identify the interesting loci and avoid using subcongenic intervals which is laborious and entailing significant time, the author combined bioinformatics and genomic strategy. On the basis of the assumption that the loci were functioning in the same or intersecting pathways, a search of the literature databases was performed to identify molecular pathways containing genes from both candidate intervals. Among the genes identified by this method were the cell cycle-associated genes Cdc25A and c-Myc, both of which have been implicated in breast cancer. Molecular and in vitro analysis showed that the polymorphisms were functionally significant. In vivo analysis was performed by generating compound PyVT/Myc double-transgenic animals to mimic the hypothetical model, and was found to recapitulate the age-of-onset phenotype. This paper provide a utilized bioinformatics way to identify that c-Myc and Cdc25A are Apmt1 and Apmt2.

Source

Genome research, Vol. 12, Issue 6, 969-975, June 2002

http://www.genome.org/cgi/content/full/12/6/969

Reference

1. Amati, B., Alevizopoulos, K., and Vlach, J. 1998. Myc and the cell cycle. Front. Biosci. 3: D250-D268

2. Falck, J., Mailand, N., Syljuasen, R.G., Bartek, J., and Lukas, J. 2001. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410: 842-847

3. Galaktionov, K., Chen, X., and Beach, D. 1996. Cdc25 cell-cycle phosphatase as a target of c-myc. Nature 382: 511-517

4. Le Voyer, T., Lu, Z., Babb, J., Lifsted, T., Williams, M., and Hunter, K. 2000. An epistatic interaction controls the latency of a transgene-induced mammary tumor. Mamm. Genome 11: 883-889

5. Lifsted, T., Le Voyer, T., Williams, M., Muller, W., Klein-Szanto, A., Buetow, K.H., and Hunter, K.W. 1998. Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int. J. Cancer 77: 640-644