title: Dominant-negative E-cadherin inhibits the invasiveness of inflammatory breast cancer cells in vitro.
abstract: E-cadherin is a transmembrane glycoprotein which mediates epithelial cell-to-cell adhesion function as a tumor suppressor and frequently loss of expression in a wide spectrum of human cancer. However, recent studies demonstrated that E-cadherin was always over-expressed in inflammatory breast cancer (IBC) specimen and cell lines, which is a clinical extreme malignancy of breast cancer. It is hypothesized that the gain and not the loss of the E-cadherin axis contributes to the IBC unique phenotype. To test this assumption, we generated dominant negative mutant E-cadherin high-expression inflammatory breast cancer cells by introduced dominant negative mutant E-cadherin (H-2kd-E-cad) cDNA into human IBC SUM149 cells. Our studies demonstrated that the ability of invasion of SUM149 cells was significantly inhibited by H-2kd-E-cad via down-regulation of MMP-1 and MMP-9 expression. The underlying signal pathway of MAPK phosphorylated Erk 1/2(P44/42) in H-2kd-E-cad-transfected SUM149 cells was significantly down-regulated compared to parental and mock contrast. Our studies provided further functional evidence as the gain of E-cadherin expression dedicated to the IBC malignant phenotype and the blockage of MAPK/Erk activation maybe a promising therapeutic target.
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Fudan University, 270 Dong'An Road, 200032, Shanghai, People's Republic of China.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Dong
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Hou
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Lu
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Luo
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009361:Neoplasm Invasiveness; D010641:Phenotype; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D018076:DNA, Complementary; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1