Regulation of IKKε Expression by Akt2 Isoform

Soumya Krishnamurthy, Alakananda Basu

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

The inhibitor of κ B kinase-ε (IKKε), a breast cancer oncogene, functions as a transforming kinase by activating NF-κB. IKKε is often elevated in breast cancers in the absence of any gene amplification. Because Akt-mediated transformation was shown to require IKKε, we examined if Akt regulates IKKε level in breast cancer cells. Knockdown of Akt2, but not other Akt isoforms, decreased the basal and TNF-induced IKKε protein and mRNA level, and overexpression of Akt2 in MDA-MB-231 cells increased IKKε level. The decrease in IKKε level by Akt2 knockdown was not only restricted to MDA-MB-231 cells but was also observed in several other breast cancer cells, including HCC1937 and MCF-10CA1a cells. Knockdown of p65/RelA subunit of NF-κB decreased IKKε level and attenuated the increase in IKKε caused by Akt2 overexpression, suggesting that Akt2-mediated induction of IKKε involves NF-κB activation. Silencing of IKKε also decreased long-term clonogenic survival of Akt2-overexpressing MDA-MB-231 cells. Taken together, these results demonstrate for the first time that IKKε functions downstream of Akt2 to promote breast cancer cell survival.

Original languageEnglish
Pages (from-to)1044-1050
Number of pages7
JournalGenes and Cancer
Volume2
Issue number11
DOIs
StatePublished - 1 Nov 2011

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Protein Isoforms
Breast Neoplasms
Phosphotransferases
Gene Amplification
Oncogenes
Cell Survival
Messenger RNA
Proteins

Keywords

  • Akt2
  • IKKε
  • NF-κB
  • TNF
  • breast cancer

Cite this

Krishnamurthy, Soumya ; Basu, Alakananda. / Regulation of IKKε Expression by Akt2 Isoform. In: Genes and Cancer. 2011 ; Vol. 2, No. 11. pp. 1044-1050.
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Regulation of IKKε Expression by Akt2 Isoform. / Krishnamurthy, Soumya; Basu, Alakananda.

In: Genes and Cancer, Vol. 2, No. 11, 01.11.2011, p. 1044-1050.

Research output: Contribution to journalArticleResearchpeer-review

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