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Integrative genomic approaches identify IKBKE as a breast cancer oncogene.

Publication ,  Journal Article
Boehm, JS; Zhao, JJ; Yao, J; Kim, SY; Firestein, R; Dunn, IF; Sjostrom, SK; Garraway, LA; Weremowicz, S; Richardson, AL; Greulich, H; Shen, RR ...
Published in: Cell
June 15, 2007

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.

Duke Scholars

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

June 15, 2007

Volume

129

Issue

6

Start / End Page

1065 / 1079

Location

United States

Related Subject Headings

  • Signal Transduction
  • Phosphatidylinositol 3-Kinases
  • NF-kappa B
  • Models, Biological
  • I-kappa B Kinase
  • Humans
  • Genomics
  • Genome
  • Gene Library
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
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Boehm, J. S., Zhao, J. J., Yao, J., Kim, S. Y., Firestein, R., Dunn, I. F., … Hahn, W. C. (2007). Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell, 129(6), 1065–1079. https://doi.org/10.1016/j.cell.2007.03.052
Boehm, Jesse S., Jean J. Zhao, Jun Yao, So Young Kim, Ron Firestein, Ian F. Dunn, Sarah K. Sjostrom, et al. “Integrative genomic approaches identify IKBKE as a breast cancer oncogene.Cell 129, no. 6 (June 15, 2007): 1065–79. https://doi.org/10.1016/j.cell.2007.03.052.
Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065–79.
Boehm, Jesse S., et al. “Integrative genomic approaches identify IKBKE as a breast cancer oncogene.Cell, vol. 129, no. 6, June 2007, pp. 1065–79. Pubmed, doi:10.1016/j.cell.2007.03.052.
Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Richardson AL, Greulich H, Stewart CJ, Mulvey LA, Shen RR, Ambrogio L, Hirozane-Kishikawa T, Hill DE, Vidal M, Meyerson M, Grenier JK, Hinkle G, Root DE, Roberts TM, Lander ES, Polyak K, Hahn WC. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065–1079.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

June 15, 2007

Volume

129

Issue

6

Start / End Page

1065 / 1079

Location

United States

Related Subject Headings

  • Signal Transduction
  • Phosphatidylinositol 3-Kinases
  • NF-kappa B
  • Models, Biological
  • I-kappa B Kinase
  • Humans
  • Genomics
  • Genome
  • Gene Library
  • Gene Expression Regulation, Neoplastic