The Use of cDNA Microarray to Study Gene Expression in Wnt1 Induced Mammary Tumors
Annual rept. 1 Jul 1998-1 Jul 1999
NATIONAL INSTITUTES OF HEALTH BETHESDA MD
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The purpose of the proposed research is to establish the cDNA microarray technology in the study of mouse mammary tumor development induced by Wnt1 proto-oncogene. We also propose to identify downstream target genes of the Wnt- 1 signaling pathway in mouse mammary epithelial C57MG cells as well as in the human kidney epithelial 293 cells. We have printed the first prints of mouse unigene cDNA microarray chips which contain about 5,000 cDNA clones. The second prints will include about 10,000 cDNA clones and is currently in preparation stage. These prints will be used to identify gene expression patterns of the normal mouse mammary gland tissue samples and mouse mammary tumor samples from the MMTV-Wnt-1 transgenic mice. Such parallel analysis of gene expression profiles may provide insights into the mechanisms underlying mouse mammary tumorigenesis and provide molecular markers for diagnosis and prognosis of mammary tumors. We are also establishing cell culture systems to acutely initiate Wnt- 1 signaling suitable for the identification of downstream target genes in the mouse mammary cells as well as in human cells. Currently, we have developed mouse mammary cell line that can be readily infected by avian leukosis virus that carry specific genes of interest such as Wnt-I. Inducible cell lines that express Wnt-1, beta-catenin, or Lef-1 proteins has also been established in the human 293 cells. These cell culture system will provide useful tools to identify downstream responsive genes of the Wnt-1 signaling pathway. These research may also provide new targets for intervention and novel strategies for treatment of mammary tumors.
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