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Mechanisms underlying differential expression of interleukin-8 in breast cancer cells.

Abstract : We have recently reported that interleukin-8 (IL-8) expression was inversely correlated to estrogen receptor (ER) status and was overexpressed in invasive breast cancer cells. In the present study, we show that IL-8 overexpression in breast cancer cells involves a higher transcriptional activity of IL-8 gene promoter. Cloning of IL-8 promoter from MDA-MB-231 and MCF-7 cells expressing high and low levels of IL-8, respectively, shows the integrity of the promoter in both cell lines. Deletion and site-directed mutagenesis of the promoter demonstrate that NF-kappaB and AP-1 and to a lesser extent C/EBP binding sites play a crucial role in the control of IL-8 promoter activity in MDA-MB-231 cells. Knockdown of NF-kappaB and AP-1 activities by adenovirus-mediated expression of an NF-kappaB super-repressor and RNA interference, respectively, decreased IL-8 expression in MDA-MB-231 cells. On the contrary, restoration of Fra-1, Fra-2, c-Jun, p50, p65, C/EBPalpha and C/EBPbeta expression levels in MCF-7 cells led to a promoter activity comparable to that observed in MDA-MB-231 cells. Our data constitute the first extensive study of IL-8 gene overexpression in breast cancer cells and suggest that the high expression of IL-8 in invasive cancer cells requires a complex cooperation between NF-kappaB, AP-1 and C/EBP transcription factors.
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https://www.hal.inserm.fr/inserm-00143639
Contributor : Gwendal Lazennec <>
Submitted on : Friday, April 27, 2007 - 9:56:41 AM
Last modification on : Sunday, December 15, 2019 - 10:20:04 PM
Long-term archiving on: : Wednesday, April 7, 2010 - 12:08:14 AM

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Ariane Freund, Valérie Jolivel, Sébastien Durand, Nathalie Kersual, Dany Chalbos, et al.. Mechanisms underlying differential expression of interleukin-8 in breast cancer cells.. Oncogene, Nature Publishing Group, 2004, 23 (36), pp.6105-14. ⟨10.1038/sj.onc.1207815⟩. ⟨inserm-00143639⟩

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