title: MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition.
abstract: Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.56%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of β-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and β-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Sang
authors.forename: C
authors.initials: C
authors.lastname: Geng
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Gu
authors.forename: B
authors.initials: B
authors.lastname: Shan
mesh_terms: D000951:Antigens, Neoplasm; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D014746:Vimentin; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D051929:CD146 Antigen; C495270:CTNNB1 protein, human; D015820:Cadherins; C497902:MCAM protein, human; D014746:Vimentin; D051176:beta Catenin
keywords: MAGE-A; breast cancer; epithelial-mesenchymal transition.; triple negative breast cancer