ABSTRACT
Immunohistochemical microarray comprising 80 patients with esophageal squamous cell carcinoma (ESCC) and discovered that the expression of CLDN1 and CLDN4 were significantly higher in cancer tissues compared to para-cancerous tissues. Furthermore, CLDN4 significantly affected the overall survival of cancer patients. When two ESCC cell lines (TE1, KYSE410) were exposed to hypoxia (0.1% O2), CLDN1/4 was shown to influence the occurrence and development of esophageal cancer. Compared with the control culture group, the cancer cells cultured under hypoxic conditions exhibited obvious changes in CLDN1 and CLDN4 expression at both the mRNA and protein levels. Through genetic intervention and Chip, we found that HIF-1α could directly regulate the expression of CLDN1 and CLDN4 in cancer cells. Hypoxia can affect the proliferation and apoptosis of cancer cells by regulating the PI3K-Akt-mTOR pathway. Molecular analysis further revealed that CLDN1 and CLDN4 can participate in the regulation process and had a feedback regulatory effect on HIF-1α expression in cancer cells. In vitro cellular experiments and vivo experiments in nude mice further revealed that changes in CLDN4 expression in cancer cells could affect the proliferation of cancer cells via regulation of Rho GTP and p-JNK pathway. Whether CLDN4 can be target for the treatment of ESCC needs further research.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Claudin-1/genetics , Claudin-1/metabolism , Claudin-1/pharmacology , Claudin-4/genetics , Claudin-4/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Feedback , Gene Expression Regulation, Neoplastic , Humans , Hypoxia/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MAP Kinase Signaling System , Mice , Mice, Nude , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/genetics , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , rho GTP-Binding Proteins/genetics , rho GTP-Binding Proteins/metabolism , rho GTP-Binding Proteins/pharmacologyABSTRACT
The current study analyzed the data of 4 000 umbilical cord blood (UCB) units collected in Shandong Cord Blood Bank from the end of 1999 to March 2001. The averages of nucleated cells and CD34(+) cells were more than 1.2 x 10(9) and 3.9 x 10(6) per UCB unit respectively, and more than 1.5 x 10(9) nucleated cells per UCB unit were obtained in 768 UCB units. These UCB units are suitable for transplantation in patients with a body weight greater than 40 kg. The analysis of HLA gene frequency showed that A2, A24, A11, B13, B51, DR15, DR7 and DR9 are the common halotypes in Shandong population and similar to those in the other areas of China. 40% patients could search out at least 1 UCB unit with 1 mismatched HLA locus in Shandong Cord Blood Bank.