title: Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis: impact of human papillomavirus infection (HPV).
abstract: OBJECTIVE
  Cervical cancer is a leading gynecological cancer in Indian women and is caused due to infection with high risk human pappilloma virus (HR-HPV) 16 and 18. It has been well documented that PML (promyelocytic leukemia) enhances viral infectivity and plays a crucial role in antiviral response mechanisms. The aim of the present study was to evaluate the role of PML gene with context to HPV infection in cervical carcinogenesis.
  
  
  METHODS
  The expression pattern of PML was analyzed by western blotting and immunohistochemistry in a total of 170 fresh surgically resected cervical tissue specimens comprising precancer (n=12), cancer (n=118) and normal controls (n=40) recruited from PGIMER, Chandigarh, India. HPV status was analyzed by L1 consensus PCR followed by type specific PCR for HR-HPV types 16 and 18 and low risk types 6 and 11.
  
  
  RESULTS
  A significant downregulation of PML protein was observed in the majority of cervical cancer and precancer cases 68% (89/130) compared to normal controls. The loss of expression pattern of PML gene was significantly increased with severity of disease both clinically and pathologically (p<0.001). HPV infection was detected in the majority of cancer cases 96% (113/118) and in 83% (10/12) of precancer lesions whereas no infection could be detected in normal controls. Interestingly, all the 68% (89/130) cervical cancer cases that showed downregulation of PML were HPV infected (p=0.0001).
  
  
  CONCLUSIONS
  Taken together, these observations suggest that the downregulation of PML gene and its synergism with HPV infection may play an important role and may serve as a new marker for early diagnosis and therapeutic intervention for cervical carcinogenesis.
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.forename: R C
authors.initials: RC
authors.lastname: Sobti
authors.forename: Vanita
authors.initials: V
authors.lastname: Suri
authors.forename: Raje
authors.initials: R
authors.lastname: Nijhawan
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.forename: B C
authors.initials: BC
authors.lastname: Das
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
mesh_terms: D016022:Case-Control Studies; D002472:Cell Transformation, Viral / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology*
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human