Cells lacking IKKα show nuclear cyclin D1 overexpression and a neoplastic phenotype: Role of IKKα as a tumor suppressor

Youn Tae Kwak, Sofyan M. Radaideh, Lianghao Ding, Rui Li, Eugene Frenkel, Michael D. Story, Luc Girard, John Minna, Udit N. Verma

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


The catalytic subunits of IκB kinase (IKK) complex, IKKα and IKKβ, are involved in activation of NF-κB and in mediating a variety of other biological functions. Though these proteins have a high-sequence homology, IKKα exhibits different functional characteristics as compared with IKKβ. Earlier, we have shown that cyclin D1 is overexpressed and predominantly localized in the nucleus of IKKα-/- cells, indicating that IKKα regulates turnover and subcellular distribution of cyclin D1, which is mediated by IKKa-induced phosphorylation of cyclin D1. Because cyclin D nuclear localization is implicated in tumor development, we examined whether the absence of IKKα leads to tumor development as well. In the current study, we show that IKKα plays a critical role in tumorigenesis. Though IKKα-/- MEF cells show a slower anchorage-dependent growth, they are clonogenic in soft agar. These cells are tumorigenic in nude mice. Microarray analysis of IKKα -/- cells indicates a differential expression of genes involved in proliferation and apoptosis. Furthermore, analysis of microarray data of human lung cancer cell lines revealed decreased IKKα RNA expression level as compared with cell lines derived from normal bronchial epithelium. These results suggest that IKKα may function as a tumor suppressor gene. Absence of IKKα may induce tumorigenicity by nuclear localization of cyclin D1 and modulating the expression of genes involved in neoplastic transformation.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalMolecular Cancer Research
Issue number3
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research


Dive into the research topics of 'Cells lacking IKKα show nuclear cyclin D1 overexpression and a neoplastic phenotype: Role of IKKα as a tumor suppressor'. Together they form a unique fingerprint.

Cite this