Dominant-negative E-cadherin inhibits the invasiveness of inflammatory breast cancer cells in vitro

• Published in: Journal of cancer research and clinical oncology 2007-02, Vol.133 (2), p.83-92
• Main Authors: DONG, Hui-Ming, GANG LIU, HOU, Yi-Feng, JIONG WU, LU, Jin-Song, LUO, Jian-Min, SHEN, Zhen-Zhou, SHAO, Zhi-Ming
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadherins - genetics; Cadherins - metabolism; Cell cycle; DNA, Complementary; Down-Regulation; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Gene expression; Genotype & phenotype; Glycoproteins; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Mutation; Neoplasm Invasiveness; Pharmacology. Drug treatments; Phenotype; Signal Transduction; Transfection; Tumor Cells, Cultured; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-006-0140-6

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.