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In situ proximity l...
In situ proximity ligation detection of c-Jun/AP-1 dimers reveals increased levels of c-Jun/Fra1 complexes in aggressive breast cancer cell lines in vitro and in vivo
- Artikel/kapitelEngelska2010
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LIBRIS-ID:oai:DiVA.org:uu-144968
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-144968URI
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https://doi.org/10.1074/mcp.M110.000943DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Genetic and biochemical studies have shown that selective interactions between the Jun, Fos, and activating transcription factor (ATF) components of transcription factor activating protein 1 (AP-1) exhibit specific and critical functions in the regulation of cell proliferation, differentiation, and survival. For instance, the ratio between c-Jun/c-Fos and c-Jun/ATF2 dimers in the cell can be a determining factor in the cellular response to oncogenic or apoptotic stimuli. Until recently, no methods were available to detect endogenous AP-1 complexes in cells and tissues in situ. Here, we validated the proximity ligation assay (PLA) for its ability to specifically visualize and quantify changes in endogenous c-Jun/c-Fos, c-Jun/ATF2, and c-Jun/Fra1 complexes by using, among others, partner-selective c-Jun mutants. Furthermore, we examined the levels of c-Jun/AP-1 dimers in cell lines representing different types of human breast cancer and found that aggressive basal-like breast cancer cells can be discriminated from much less invasive luminal-like cells by PLA detection of c-Jun/Fra1 rather than of c-Jun/ATF2 and c-Jun/c-Fos. Also in tumor tissue derived from highly metastatic basal-like MDA-MB231 cells, high levels of c-Jun/Fra1 complexes were detected. Together, these results demonstrate that in situ PLA is a powerful diagnostic tool to analyze and quantify the amounts of biologically critical AP-1 dimers in fixed cells and tissue material.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Pardali, Evangelia
(författare)
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ten Dijke, PeterUppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)pedij839
(författare)
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van Dam, Hans
(författare)
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Uppsala universitetLudwiginstitutet för cancerforskning
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Molecular & Cellular Proteomics9:9, s. 1982-19901535-94761535-9484
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