Integrative genomic approaches identify IKBKE as a breast cancer oncogene.

@article{citeulike:1616351, abstract = {Addgene: The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKepsilon), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKKepsilon expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKKepsilon activates the nuclear factor-kappaB (NF-kappaB) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF-kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery.}, address = {Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.}, author = {Boehm, J. S. and Zhao, J. J. and Yao, J. and Kim, S. Y. and Firestein, R. and Dunn, I. F. and Sjostrom, S. K. and Garraway, L. A. and Weremowicz, S. and Richardson, A. L. and Greulich, H. and Stewart, C. J. and Mulvey, L. A. and Shen, R. R. and Ambrogio, L. and Hirozane-Kishikawa, T. and Hill, D. E. and Vidal, M. and Meyerson, M. and Grenier, J. K. and Hinkle, G. and Root, D. E. and Roberts, T. M. and Lander, E. S. and Polyak, K. and Hahn, W. C. }, citeulike-article-id = {1616351}, doi = {10.1016/j.cell.2007.03.052}, issn = {0092-8674}, journal = {Cell}, keywords = {plasmid}, month = {June}, number = {6}, pages = {1065--1079}, posted-at = {2008-02-03 16:02:32}, priority = {2}, title = {Integrative genomic approaches identify IKBKE as a breast cancer oncogene.}, url = {http://dx.doi.org/10.1016/j.cell.2007.03.052}, volume = {129}, year = {2007} }

TY - JOUR ID - citeulike:1616351 L3 - citeulike-article-id:1616351 TI - Integrative genomic approaches identify IKBKE as a breast cancer oncogene. JF - Cell VL - 129 IS - 6 SP - 1065 EP - 1079 AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. SN - 0092-8674 N2 - Addgene: The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKepsilon), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKKepsilon expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKKepsilon activates the nuclear factor-kappaB (NF-kappaB) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF-kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery. KW - plasmid AU - Boehm, JS AU - Zhao, JJ AU - Yao, J AU - Kim, SY AU - Firestein, R AU - Dunn, IF AU - Sjostrom, SK AU - Garraway, LA AU - Weremowicz, S AU - Richardson, AL AU - Greulich, H AU - Stewart, CJ AU - Mulvey, LA AU - Shen, RR AU - Ambrogio, L AU - Hirozane-Kishikawa, T AU - Hill, DE AU - Vidal, M AU - Meyerson, M AU - Grenier, JK AU - Hinkle, G AU - Root, DE AU - Roberts, TM AU - Lander, ES AU - Polyak, K AU - Hahn, WC PY - 2007/06/15/ UR - http://dx.doi.org/10.1016/j.cell.2007.03.052 ER -