title: Aberrant promoter methylation and loss of suppressor of cytokine signalling-1 gene expression in the development of uterine cervical carcinogenesis.
abstract: BACKGROUND
  Cervical cancer is a leading cause of cancer related deaths in women worldwide caused due to infection of high-risk human papillomaviruses. As JAK/STAT signalling pathway has been shown to play an important role during carcinogenesis, we studied the role of silencing of Suppressor of Cytokine Signalling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway in cervical cancer.
  
  
  METHODS
  The expression pattern of SOCS-1 mRNA and protein was analyzed in different stages of cervical tumor biopsies while normal cervical tissues served as controls. RT-PCR, immunohistochemistry and methylation-specific PCR (MSP) were performed to assess the expression pattern and promoter methylation of SOCS-1 gene in a total of 120 fresh surgically resected cervical tissue specimens comprising precancer (n = 12), cancer (n = 78) and normal controls (n = 30).
  
  
  RESULTS
  Compared with expression of SOCS-1 in normal tissues, 64% of the tumor tissues expressed either undetectable or reduced expression. Aberrant promoter methylation of SOCS-1 was found in 61% of the cervical tumor tissues. SOCS-1 expression and methylation were significantly associated with severity of the disease (p < 0.01).
  
  
  CONCLUSIONS
  We demonstrate for the first time the transcriptional inactivation of SOCS-1 gene due to hypermethylation and synergism with HPV infection which may play an important role in cervical carcinoma.
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh, India. rcsobti@pu.ac.in
authors.forename: R C
authors.initials: RC
authors.lastname: Sobti
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.forename: Vanita
authors.initials: V
authors.lastname: Suri
authors.forename: Raje
authors.initials: R
authors.lastname: Nijhawan
authors.forename: A C
authors.initials: AC
authors.lastname: Bharti
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: B C
authors.initials: BC
authors.lastname: Das
mesh_terms: D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000821:virology
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins