title: Clinical significance of inactivated glycogen synthase kinase 3β in HPV-associated cervical cancer: Relationship with Wnt/β-catenin pathway activation.
abstract: OBJECTIVE
  To determine the role of inactivated GSK3β with respect to Wnt/β-catenin pathway activation in HPV-16/18-associated cervical cancer.
  
  
  METHODS
  The expression of active (pGSK3β-Try(216)), inactive (pGSK3β-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with β-catenin and APC expression.
  
  
  RESULTS
  The dramatic decrease of pGSK3β-Try(216) expression but ectopic overexpression of pGSK3β-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P = 0.0001; P = 0.001) and also positively correlated with nuclear β-catenin (P = 0.0001; P = 0.0001).
  
  
  CONCLUSIONS
  The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3β inactivation and overactivation of Wnt/β-catenin pathway.
authors.affiliation: Department of Anatomy, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Rath
authors.forename: Poonam
authors.initials: P
authors.lastname: Jawanjal
authors.forename: Sudha
authors.initials: S
authors.lastname: Salhan
authors.forename: Manoharan
authors.initials: M
authors.lastname: Nalliah
authors.forename: Indrani
authors.initials: I
authors.lastname: Dhawan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Cervical intra-epithelial neoplasia; HPV-16/18; Wnt/β-catenin pathway; c-Myc; pGSK3β-Try216/pGSK3β-Ser9; squamous cell carcinoma