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Access through your institution Buy or subscribe > ....the expression of inflammatory mediators can help to maintain > growth arrest. Jesús Gil and colleagues instigated a short
hairpin RNA inhibition screen to look for genes whose knockdown can extend the proliferative lifespan of near-senescent primary human fibroblasts. Among the genes that were identified was
the chemokine-encoding _CXCR2_ (also known as _IL8RB_ ). Knockdown of _CXCR2_ was shown to extend the replicative lifespan of several primary cells as well as fibroblasts that had undergone
oncogene-induced senescence (OIS) owing to the expression of the kinase MEK1. Levels of expression of CXCR2 were shown to increase as cells underwent either replicative senescence or OIS, so
Gil and colleagues asked whether similar alterations were evident in chemokines that bind CXCR2. Antibody arrays, ELISA and quantitative reverse transcription PCR showed that expression of
CXCR2 ligands, including interleukin 8 (IL8), were increased in cells undergoing OIS. Importantly, the authors also found that increased staining for CXCR2 is evident in samples of human
prostate intraepithelial neoplasia, which are associated with high levels of senescent cells, and CXCR2 staining levels decreased in more advanced disease. What induces expression of these
ligands? By using several chemical inhibitors and analysing transcription factor binding sites within the promoters of these ligands, the authors established the involvement of both NFκB and
C/EBPβ. Knockdown of either of these transcription factors suppressed expression of IL8, and both factors bind the _IL8_ promoter. This is a preview of subscription content, access via your
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article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in
* Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH PAPERS * Acosta, J. C. et al. Chemokine signaling via the CXCR2 receptor reinforces
senescence. _Cell_ 133, 1006–1018 (2008) Article CAS Google Scholar * Kuilman, T. et al. Oncogene induced senescence relayed by an interleukin-dependent inflammatory network. _Cell_ 133,
1019–1031 (2008) Article CAS Google Scholar Download references Authors * Nicola McCarthy View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE McCarthy, N. Hold that thought. _Nat Rev Cancer_ 8, 489 (2008). https://doi.org/10.1038/nrc2429 Download citation *
Issue Date: July 2008 * DOI: https://doi.org/10.1038/nrc2429 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a
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