Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast

摘要: Claudins are transmembrane proteins that seal tight junctions, and critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role cancer progression remains largely unexplored. Here, we report Claudin-7 (CLDN-7) expression is lower invasive ductal carcinomas (IDC) of the breast than normal epithelium, as determined by both RT-PCR (9/10) Western analysis (6/8). Immunohistochemical (IHC) carcinoma situ (DCIS) IDC showed loss CLDN-7 correlated with histological grade DCIS (P<0.001, n=38) (P=0.014, n=31), occurring predominantly high-grade (Nuclear Elston 3) lesions. Tissue array 355 cases further confirmed inverse correlation between (P=0.03). This pattern consistent biological function CLDN-7, greater discohesion typically observed In line this observation, IHC analysis, was lost vast majority (13/17) lobular situ, which defined cellular discohesion. fact, inducing disassociation MCF-7 T47D cells culture treating HGF/scatter factor resulted a within 24 h. Silencing promoter hypermethylation methylation-specific PCR (MSP) nucleotide sequencing lines (3/3), but not IDCs (0/5). summary, these studies provide insight into potential ability to disseminate.