Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer.
Bibliographical noteFunding Information:
We thank Fred Miller and S.J. Santner for providing human breast cell lines kindly. This work was supported by Research Program for New Drug Target Discovery (No. M10601000116-07N0100-11610) grant from the Ministry of Education, Science & Technology, and in part by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (MOEST) [No. R01-2007-000-20047-0 (2007)]. In addition, this work was supported by the National Cancer Center Research Grants (0510050) to Y.K.J. and partly by University Research Fund of 2007 (No. 2007-7-0178) and by the Brain Korea21 (BK21) Program. D.K.R is fellowship awardee by BK21 Program.
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