title: Expression and inactivation of glycogen synthase kinase 3 alpha/ beta and their association with the expression of cyclin D1 and p53 in oral squamous cell carcinoma progression.
abstract: BACKGROUND
  The study aims to evaluate the expression and activity of glycogen synthase kinase 3 isoforms α/β (GSK3α/β) and to assess their oncogenic potential through a correlation with the expression of cyclin D1 and p53 in oral cancer.
  
  
  METHODS
  The expression of total and phosphorylated GSK3α/β as well as cyclin D1 and p53 together with their interaction were assessed in human oral cancer tissue samples, apparently normal adjacent tissues, benign tumor samples, premalignant lesions and healthy normal tissues (total 179) using various methods, such as immunohistochemistry, Western blot assays, immunoprecipitation and RT-PCR analysis.
  
  
  RESULTS
  The expression of GSK3β was significantly higher relative to GSK3α indicating the greater role of the β isoform in oral cancer. Among various types of oral cancers, OSCC (of the lip and tongue) showed elevated expression of GSK3α/β, and the expression was correlated with disease progression. The increased expression of pS(21)GSK3α and pS(9)GSK3β not only correlated positively with cyclin D1 and p53 expression in tongue cancer progression but a gradual shift of their expression from the cytoplasmic to the nuclear compartment and overall disease severity was also observed. The interaction of GSK3β-cyclin D1 and the positive correlation of pS(9)GSK3β and the transcription of cyclin D1 were observed.
  
  
  CONCLUSIONS
  These results demonstrate that the inactivation of GSK3β is an important event in OSCC and can be used as a marker for assessing disease severity and may be exploited for therapeutic intervention.
authors: Centre for Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ratu-Lohardaga Road, Brambe, Ranchi, 835205, Jharkhand, INDIA. mishrark1@yahoo.co.in.
authors: Rajakishore
authors: R
authors: Mishra
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, INDIA. snlabau@gmail.com.
authors: Siddavaram
authors: S
authors: Nagini
authors: Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, 2160 South First Ave., Maywood, 60153, IL, USA. arana@lumc.edu.
authors: Ajay
authors: A
authors: Rana
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C530104:CCND1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha
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