Document Detail


The rotamase Pin1 is up-regulated, hypophosphorylated and required for cell cycle progression in head and neck squamous cell carcinomas.
MedLine Citation:
PMID:  19502098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The peptidyl-prolyl cis/trans isomerase Pin1 has been implicated in malignant transformation in multiple studies, however, little is known about its potential impact in head and neck cancer. This study evaluates the role of Pin1 in head and neck squamous cell carcinomas (HNSCCs). Pin1 expression and level of phosphorylation was evaluated by Western blot analysis and 2D-gel-electrophoresis. Pin1 was inhibited with juglone (5-hydroxy-1,4-naphthalenedione) or Pin1 specific siRNA and its influence on cell cycle checkpoint distribution was assessed by FACS analysis. Pin1 overexpression was found in HNSCC tissues and cell lines. 2D-gel-electrophoresis data pointed to Pin1 being hypophosphorylated in HNSCC cells which is consistent with overactivation of this rotamase. Inhibition of HNSCC cells with juglone or Pin1 siRNA induced the cell cycle inhibitor p21(WAF1/Cip1) with a concomitant reduction of cells in G2/M and an increased fraction of cells with fragmented DNA. Cell death did not correlate with significant levels of apoptosis in Pin1 depleted HNSCC cells. In summary, the data shows that Pin1 is overexpressed and hypophosphorylated in HNSCC, and that inhibition of Pin1 blocks cell cycle progression and triggers tumor cell death. Pin1 therefore could represent a new target for the development of improved HNSCC targeting drugs.
Authors:
Susanne Wiegand; Branka Dakic; Ariane F E Rath; Galina Makarova; Carolina Sterz; Wolfgang Meissner; Michael Bette; Jürgen Adamkiewicz; Sabine Müller-Brüsselbach; Rolf Müller; Jochen A Werner; Robert Mandic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-06
Journal Detail:
Title:  Oral oncology     Volume:  45     ISSN:  1879-0593     ISO Abbreviation:  Oral Oncol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-23     Completed Date:  2011-03-16     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  e140-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Alkaline Phosphatase / pharmacology
Apoptosis
Blotting, Western
Carcinoma, Squamous Cell / metabolism*
Case-Control Studies
Cell Cycle / physiology
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Electrophoresis, Gel, Two-Dimensional
Enzyme Inhibitors / pharmacology
Female
Head and Neck Neoplasms / metabolism*
Humans
Male
Middle Aged
Naphthoquinones / pharmacology
Neoplasm Proteins / metabolism*
Peptidylprolyl Isomerase / antagonists & inhibitors,  metabolism*
Phosphorylation
RNA, Small Interfering / pharmacology
Up-Regulation
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Enzyme Inhibitors; 0/NIMA-interacting peptidylprolyl isomerase; 0/Naphthoquinones; 0/Neoplasm Proteins; 0/RNA, Small Interfering; EC 3.1.3.1/Alkaline Phosphatase; EC 5.2.1.8/Peptidylprolyl Isomerase; W6Q80SK9L6/juglone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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