title: Up-regulation of plakophilin-2 and Down-regulation of plakophilin-3 are correlated with invasiveness in bladder cancer.
abstract: OBJECTIVE
  To examine plakophilin proteins (Pkp) and 3 expression levels in bladder cancer, in particular their levels during cellular growth and invasion. Pkp is associated with the binding of cadherin to intermediate filaments of the cytoskeleton.
  
  
  METHODS
  The relative mRNA and protein expression levels of Pkp2 and 3 in bladder cancer cell lines were determined using quantitative real-time polymerase chain reaction and Western blot analyses. The cellular localization of Pkp2 and 3 proteins in bladder cancer cells was also assayed using immunohistochemistry. The proliferation and invasive activities of bladder cancer cells were evaluated using cell growth and in vitro cell invasion assays, and were compared with those of bladder cancer cells treated with Pkp2 and 3 small interfering RNAs.
  
  
  RESULTS
  Pkp2 mRNA and protein levels were elevated, and those of Pkp3 were reduced, in bladder cancer cells that are known to exhibit increased proliferation and invasive activity. Pkp2/3 protein expression was predominantly observed in the cytoplasm of invasive bladder cancer cells and tissues. Pkp2 knockdown inhibited, and Pkp3 knockdown enhanced, invasion of bladder cancer cells, but these knockdowns did not alter cell proliferation.
  
  
  CONCLUSIONS
  We conclude that high Pkp2, and low Pkp3, expression is associated with bladder cancer cell invasion and that neither Pkp2 nor Pkp3 is associated with cell proliferation. We further hypothesize that accumulation of Pkp2 and 3 in the cell cytoplasm, rather than their recruitment to the cell membrane, is related to an increased ability of the tumor to invade and metastasize.
authors: Department of Urology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors: Hisaya
authors: H
authors: Takahashi
authors: Hiroyoshi
authors: H
authors: Nakatsuji
authors: Masayuki
authors: M
authors: Takahashi
authors: Shiirevnyamba
authors: S
authors: Avirmed
authors: Tomoya
authors: T
authors: Fukawa
authors: Masahiko
authors: M
authors: Takemura
authors: Tomoharu
authors: T
authors: Fukumori
authors: Hiroomi
authors: H
authors: Kanayama
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000235:genetics; D051191:Plakophilins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051191:Plakophilins; D012333:RNA, Messenger