10.1021/pr900430n.s010 Simin Lim Simin Lim Lee-Yee Choong Lee-Yee Choong Chong Poh Kuan Chong Poh Kuan Chen Yunhao Chen Yunhao Yoon-Pin Lim Yoon-Pin Lim Regulation of Macrophage Inhibitory Factor (MIF) by Epidermal Growth Factor Receptor (EGFR) in the MCF10AT Model of Breast Cancer Progression American Chemical Society 2009 breast cancer development 3CA PIK Breast Cancer ProgressionGenetic aberration Epidermal Growth Factor Receptor EGF stimulation grade cancer cells MCF 10AT preneoplastic MCF 10CA MIF expression level MCF 10AT Model DIGE MCF 10AT system 4 isogenic cell lines CA 1h breast cancer cells expression level Macrophage Inhibitory Factor MIF expression levels grade breast cancer cells MEK breast cancer progression EGFR EGF treatment MCF 10AT model 2009-08-07 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Regulation_of_Macrophage_Inhibitory_Factor_MIF_by_Epidermal_Growth_Factor_Receptor_EGFR_in_the_MCF10AT_Model_of_Breast_Cancer_Progression/2837812 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.