title: Involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation.
abstract: Dissociation of pancreatic cancer cells from primary sites is the critical first step in tumour invasion and metastasis. Changes in the structure and function of tight junctions are reported to be correlated with carcinogenesis and tumour development. Using cDNA microarray analysis, we recently identified claudin-23 as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells. In this study, RT-PCR, Western blotting and immunocytochemistry were used to demonstrate the involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation. Claudin-23 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Claudin-23 expression was induced in a PC-1.0 subclone expressing mitogen-activated protein kinase kinase (MEK)-1 short-hairpin RNA (shRNA) and claudin-23 was redistributed in a PC-1.0 subclone expressing MEK2 shRNA. Furthermore, these MEK2 shRNA-expressing PC-1.0 cells aggregated and formed island-like cell colonies. By contrast, the addition of dissociation factor-conditioned medium significantly reduced claudin-23 mRNA and protein expression in PC-1 cells. The present results indicate that claudin-23 is involved in the regulation of pancreatic cancer cell dissociation through changes in gene expression and intracellular localisation. In addition, claudin-23 expression is possibly correlated with the activation of the MEK signalling pathway during pancreatic cancer cell dissociation. Claudin-23 may thus serve as a new target for molecular therapies to prevent pancreatic cancer invasion and metastasis.
authors.affiliation: Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang 110004, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xianwei
authors.initials: X
authors.lastname: Dai