PMID- 22957302
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20211021
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 2
IP  - 5
DP  - 2012
TI  - PAR6B is required for tight junction formation and activated PKCzeta localization in 
      breast cancer.
PG  - 478-91
AB  - Dysregulation of mechanisms that govern the control of epithelial cell polarity, 
      morphology and plasticity are emerging as key processes in tumor progression. In 
      this study we report amplification and overexpression of PAR6B, an essential 
      component in epithelial cell tight junction (TJ) formation and maintenance of 
      apico-basal polarity, in breast cancer cell lines. Analysis of chromosome 
      20q13.13 in 11 breast cancer cell lines by fluorescence in situ hybridization 
      (FISH) identified a novel small amplicon centered at PARD6B in 5 cell lines, with 
      copy number ranging from 7 to 27. The presence of the PARD6B amplicon correlated 
      with PARD6B transcript and PAR6B protein abundance. Expression of related 
      isoforms PARD6A and PARD6G were detectable at significantly lower levels. PARD6B 
      overexpression correlated with TJ network formation in cultured cell monolayers. 
      SiRNA-mediated inhibition of PAR6B in MCF7 resulted in loss of TJ assembly and 
      membrane localization of atypical PKCzeta (aPKC), but did not affect adherens 
      junction formation. SiRNA-mediated inhibition of CDC42 in MCF7 also resulted in 
      loss of TJ networks, confirming the requirement of a complete 
      PAR6-aPKC-CDC42-PAR3 complex to activate and stabilize TJs. Immunohistochemical 
      analysis of PAR6B expression on breast tumor microarrays indicated exquisite 
      epithelial cell-specificity. Few quantitative differences in staining were 
      observed between normal epithelium and adjacent tumor margins. However staining 
      appeared reduced and cytoplasmic in more poorly differentiated tumors. We propose 
      that quantitative imbalances in the components of pathways governing normal 
      epithelial cell polarity arising from gain or loss of function may radically 
      alter epithelial cell architecture and contribute to tumor progression.
FAU - Cunliffe, Heather E
AU  - Cunliffe HE
FAU - Jiang, Yuan
AU  - Jiang Y
FAU - Fornace, Kimberly M
AU  - Fornace KM
FAU - Yang, Fan
AU  - Yang F
FAU - Meltzer, Paul S
AU  - Meltzer PS
LA  - eng
PT  - Journal Article
DEP - 20120820
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC3433109
OTO - NOTNLM
OT  - Breast Cancer
OT  - CDC42
OT  - DNA amplification
OT  - PAR6B
OT  - PARD6B
OT  - PKCzeta
OT  - adhesion
OT  - polarity
OT  - siRNA
OT  - tight junction
EDAT- 2012/09/08 06:00
MHDA- 2012/09/08 06:01
PMCR- 2012/08/20
CRDT- 2012/09/08 06:00
PHST- 2012/06/01 00:00 [received]
PHST- 2012/07/11 00:00 [accepted]
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2012/09/08 06:01 [medline]
PHST- 2012/08/20 00:00 [pmc-release]
PST - ppublish
SO  - Am J Cancer Res. 2012;2(5):478-91. Epub 2012 Aug 20.