Gene Expression Profiling of Breast Cancers with Emphasis of beta-Catenin Regulation

ABSTRACT

To gain molecular understanding of carcinogenesis of breast cancer, gene expression profiles were analyzed using cDNA microarray representing 4,600 cDNAs in 10 breast cancer samples and the adjacent noncancerous breast tissues from the same patients. The alterations in gene expression levels were confirmed by reversetranscription PCR in four randomly selected genes. Genes that were differently expressed in cancer and noncancerous tissues were identified. 106 (of which 55 were known) and 49 (of which 28 were known) genes were up- or down-regulated, respectively, in greater than 60% of the breast cancer samples. In cancer tissues, genes related to cell cycle, transcription, metabolism, cell structure/motility and signal transduction were mostly up-regulated. Furthermore, three cancer tissues showing immunohistochemically aberrant accumulation of beta-catenin in the nucleus and/or cytoplasm revealed down-regulation of Siah and Axin genes and up-regulation of Wnt and c-myc genes. These findings were highly consistent with Wnt signaling pathway associated with beta-catenin regulation previously suggested by others. Our studies, therefore, provide not only a molecular basis to understand biological processes of breast cancer but also useful resources to define the mechanism of beta-catenin expression in tumorigenesis of breast cancer.