Regulation of macrophage inhibitory factor (MIF) by epidermal growth factor receptor (EGFR) in the MCF10AT model of breast cancer progression
- PMID: 19530702
- DOI: 10.1021/pr900430n
Regulation of macrophage inhibitory factor (MIF) by epidermal growth factor receptor (EGFR) in the MCF10AT model of breast cancer progression
Abstract
Genetic aberration of EGFR is one of the major molecular characteristics of breast cancer. However, the molecular changes associated with EGFR signaling during different stages of breast cancer development have not been studied. In this study, complementary two-dimensional-DIGE and iTRAQ technologies were used to profile the expression level of proteins in 4 isogenic cell lines in the MCF10AT model of breast cancer progression following a time course of EGF stimulation. A total of 80 proteins (67 from iTRAQ, 15 from DIGE, 2 common in both) were identified to be up- or down-regulated by EGF treatment. Following EGF stimulation, the expression level of MIF, a cytokine that has been implicated in many human cancers, was decreased in MCF10A1 normal breast mammary epithelial cells, increased in MCF10AT1k preneoplastic and MCF10CA1h low grade breast cancer cells, but showed no obvious difference in the MCF10CA1a high grade cancer cells. The increase in MIF expression level following EGF treatment could also be observed in A431 cervical cancer cells. EGF-induced increases of MIF expression levels in CA1h breast cancer cells were abrogated when MEK, but not PIK3CA, was knocked down. In addition, silencing of MIF diminished the proliferation of EGF-stimulated CA1h cells when compared to control cells. Taken together, our data suggested an EGFR --> MEK --> MIF proliferative pathway that has never been reported previously and that this pathway "evolves" during disease progression as modeled by the MCF10AT system. Revelation of the novel relationship between MIF and EGF may contribute to an integrated understanding of the roles of these oncogenic factors during breast cancer development.
Similar articles
-
Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib.PLoS One. 2015 May 13;10(5):e0125232. doi: 10.1371/journal.pone.0125232. eCollection 2015. PLoS One. 2015. PMID: 25969993 Free PMC article.
-
Overexpression of macrophage migration inhibitory factor induces angiogenesis in human breast cancer.Cancer Lett. 2008 Mar 18;261(2):147-57. doi: 10.1016/j.canlet.2007.11.028. Epub 2008 Jan 2. Cancer Lett. 2008. PMID: 18171602
-
Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells.Oncogene. 2006 Dec 7;25(58):7565-76. doi: 10.1038/sj.onc.1209740. Epub 2006 Jun 19. Oncogene. 2006. PMID: 16785991
-
Macrophage migration inhibitory factor involvement in breast cancer (Review).Int J Oncol. 2015 Nov;47(5):1627-33. doi: 10.3892/ijo.2015.3185. Epub 2015 Sep 24. Int J Oncol. 2015. PMID: 26412712 Free PMC article. Review.
-
Epidermal growth factor signaling in transformed cells.Int Rev Cell Mol Biol. 2015;314:1-41. doi: 10.1016/bs.ircmb.2014.10.001. Epub 2014 Nov 18. Int Rev Cell Mol Biol. 2015. PMID: 25619714 Free PMC article. Review.
Cited by
-
Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging.J Proteome Res. 2012 Dec 7;11(12):5736-47. doi: 10.1021/pr300555y. Epub 2012 Nov 26. J Proteome Res. 2012. PMID: 23116296 Free PMC article.
-
Integrated proteomic and metabolic analysis of breast cancer progression.PLoS One. 2013 Sep 27;8(9):e76220. doi: 10.1371/journal.pone.0076220. eCollection 2013. PLoS One. 2013. PMID: 24086712 Free PMC article.
-
Evaluation of global differential gene and protein expression in primary Pterygium: S100A8 and S100A9 as possible drivers of a signaling network.PLoS One. 2014 May 13;9(5):e97402. doi: 10.1371/journal.pone.0097402. eCollection 2014. PLoS One. 2014. PMID: 24825356 Free PMC article.
-
Proteome-wide profiling of the MCF10AT breast cancer progression model.PLoS One. 2010 Jun 9;5(6):e11030. doi: 10.1371/journal.pone.0011030. PLoS One. 2010. PMID: 20543960 Free PMC article.
-
Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74.J Am Soc Nephrol. 2016 Jun;27(6):1650-64. doi: 10.1681/ASN.2015020149. Epub 2015 Oct 9. J Am Soc Nephrol. 2016. PMID: 26453615 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous