title: Decreased expression of human papillomavirus E2 protein and transforming growth factor-beta1 in human cervical neoplasia as an early marker in carcinogenesis.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is thought to be one of the possible causative factors in cervical carcinogenesis, and cervical carcinoma cells are refractory to tumor transforming growth factor (TGF)-beta1. The purpose of this study is to investigate the possible cause-effect association between HPV and TGF-beta1 during cervical tumorigenesis.
  
  
  METHODS
  We assessed the expression of HPV capsid proteins, HPV-16 E7, HPV-16 E2 (C and N terminals), TGF-beta1, and their receptors TGF-beta RI and RII by immunohistochemistry in 48 paraffin-embedded blocks of tumor tissue derived from patients of cervical neoplasia.
  
  
  RESULTS
  Expression of TGF-beta1 decreased as tumor cells progressed from cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, to microinvasive carcinoma (P < 0.05). Levels of TGF-betaRI and TGFbeta-RII stayed the same in all cases. HPV was found in 89.6% of the studied sections, and cervical lesions without HPV infection expressed significantly less TGF-beta1 (P < 0.05). By comparing the expression pattern of TGF-beta1 and HPV in the neoplastic cells with that of normal cervical epithelium in each section, we found loss of HPV-16 E2 higher in CIN3 (15/24) than in CIN1 or CIN2 (3/7), and there is a significant trend that loss of HPV-16 E2 expression correlated with a >50% loss of TGF-beta1 at the lesion site (P < 0.05).
  
  
  CONCLUSIONS
  Our result showed co-suppression of HPV and TGF-beta1 expression during progression of cervical squamous cell cancer. Using antibody against HPV-16 E2 may be an auxiliary tool for the investigation of cervical tumor progression.
authors.affiliation: The Department of Obstetrics & Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan. pltorng@ha.mc.ntu.edu.tw
authors.forename: Pao-Ling
authors.initials: PL
authors.lastname: Torng
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Chan
authors.forename: Chin-Tang
authors.initials: CT
authors.lastname: Lin
authors.forename: Su-Cheng
authors.initials: SC
authors.lastname: Huang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000821:virology; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D014412:Tumor Virus Infections / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1