Use of cDNA Microarray to Study Gene Expression in Wnt-1 Induced Mammary Tumors

摘要

To understand the multi-step process of mammary tumorigenesis, we have compared gene expression profiles in different stages of mammary oncogenesis in MMTV-Wnt- 1 transgenic mice. Specifically, we have collected tissue samples from virgin mammary glands, hyperplastic mammary glands, Wnt- 1 mammary tumors, and tumors metastasized to the lung, and compared their gene expression patterns. Hierarchical clustering analysis and multidimensional scaling analysis showed that gene expression profiles are associated with tumor progression. Each sample group from the same stage cluster separately from samples at other stages. Using the statistical analysis permutation t-test, I identified groups of genes differentially expressed in each of the stages. I also identified a group of genes as potential direct or indirect target genes of Wnt signaling since they are only regulated in mammary tumors induced by the MMTV-Wnt-1 transgene in comparison with tumors induced by other transgenes such as (MMTV)-c-myc, MMTV-Ha-ras, MMTV-neu, MMTV-polyoma middle T antigen, C3(l)/ simian virus 40 T/t antigen, and WAP-SV4O T/t antigen (Desai et al., 2002). In addition, I established gene expression profiles for mammary tumors induced by Wntl, and by Wnt1 in cooperation with loss of tumor suppressor genes such as Pten or P53.