title: Characterization of Toll-like receptor transcriptome in squamous cell carcinoma of cervix: A case-control study.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC).
  
  
  METHODS
  Gene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting.
  
  
  RESULTS
  HPV was detected in all cases and in none of the controls (p<0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p<0.0001), TLR4 (p<0.0005) and TLR5 (p<0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p=0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies.
  
  
  CONCLUSIONS
  A significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: ritu_immunopath@yahoo.co.in.
authors.forename: Ritu
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sunayana
authors.initials: S
authors.lastname: Misra
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Charu
authors.initials: C
authors.lastname: Guleria
authors.affiliation: Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vanita
authors.initials: V
authors.lastname: Suri
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Mangat
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Raje
authors.initials: R
authors.lastname: Nijhawan
authors.affiliation: Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Minz
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology; D011446:Prospective Studies; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: D051193:Toll-Like Receptors
keywords: Cervical cancer; Human papillomavirus; India; Polymerase chain reaction; TLR; Toll like receptors