Whole Genome Expression Profiling Reveals a Significant Role for the Cell Junction and Apoptosis Pathways in Breast Cancer Stem Cells
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Side population (SP) cells in primary tumors and cell lines are a small cell population, but they are known to enrich cancer stem cells (CSCs). In this study, we isolated SP cells from the human breast cancer cell line MCF7 as a model for studying CSCs. Compared with non-SP cells, MCF7 SP cells had higher mammosphere-formation efficiency (MFE) in vitro and greater tumorigenicity in vivo, suggesting that MCF7 SP cells enrich CSCs. We first directly compared the gene expression profile of SP and non-SP cells from MCF7 cell line. Comparing the expression signature of SP to non-SP cells, we identified 753 differentially expressed genes (DEGs). Using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified multiple pathways that were aberrantly regulated in SP compared with non-SP cells. Several pathways, including cell junction and apoptosis, play important roles in breast CSC function. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources can enhance our understanding of the critical pathways that regulate breast CSCs.
KeywordsBreast neoplasm Cancer stem cells Side population cells Microarray Gene regulatory networks
The authors thank to ZhongXin Biotechnology (Shanghai, China) for the help of microarray analysis. This study was supported in part by the grant from National Natural Science Fund of China (30670798).
- 12.Hirschmann-Jax, C., Foster, A. E., Wulf, G. G., Nuchtern, J. G., Jax, T. W., Gobel, U., et al. (2004). A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proceedings of the National Academy of Sciences of the United States of America, 101, 14228–14233.CrossRefGoogle Scholar
- 19.Zhou, J., Wulfkuhle, J., Zhang, H., Gu, P., Yang, Y., Deng, J., et al. (2007). Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proceedings of the National Academy of Sciences of the United States of America, 104, 16158–16163.CrossRefGoogle Scholar
- 30.Thom, I., Schult-Kronefeld, O., Burkholder, I., Schuch, G., Andritzky, B., Kastendieck, H., et al. (2009). Expression of CEACAM-1 in pulmonary adenocarcinomas and their metastases. Anticancer Research, 29, 249–254.Google Scholar
- 31.Madjd, Z., Mehrjerdi, A. Z., Sharifi, A. M., Molanaei, S., Shahzadi, S. Z., & Asadi-Lari, M. (2009). CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours. Cancer Immunity, 9, 4.Google Scholar