PMID: 11325857Apr 28, 2001Paper

Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor-kappaB in breast cancer

Cancer Research
R Romieu-MourezG E Sonenshein

Abstract

Nuclear factor-kappaB (NF-kappaB)/Rel transcription factors regulate genes that control cell proliferation, survival, and transformation. In normal breast epithelial cells, NF-kappaB/Rel proteins are mainly sequestered in the cytoplasm bound to one of the specific inhibitory IkappaB proteins, whereas in breast cancers they are activated aberrantly. Human breast tumor cell lines, carcinogen-transformed mammary epithelial cells, and the majority of primary human or rodent breast tumor tissue samples express constitutively high levels of nuclear NF-kappaB/REL: To begin to understand the mechanism of this aberrant NF-kappaB/Rel expression, in this study we measured the activity of the major kinases implicated in regulation of IkappaB stability, namely IKKalpha, IKKbeta, and protein kinase, CK2 (formerly casein kinase II). Hs578T, D3-1, and BP-1 breast cancer cell lines displayed higher levels of IKKalpha, IKKbeta, and CK2 activity than untransformed MCF-10F mammary epithelial cells. Inhibition of IKK activity upon expression of dominant negative kinases or of CK2 activity by treatment with selective inhibitors decreased NF-kappaB/Rel activity in breast cancer cells. Inactivation of the IkappaB kinase complex in Hs578T cells via exp...Continue Reading

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