Down-regulation of GATA-3 expression during human papillomavirus-mediated immortalization and cervical carcinogenesis

Am J Pathol. 2002 Jun;160(6):1945-51. doi: 10.1016/S0002-9440(10)61143-1.


To identify cellular genes that may be involved in human papillomavirus (HPV)-mediated immortalization mRNA differential display analysis was performed on preimmortal and subsequent immortal stages of four human keratinocyte cell lines transformed by HPV type 16 or 18 DNA. This yielded a cDNA fragment encoding the transcription factor GATA-3 that was strongly reduced in intensity in all immortal stages of the four cell lines. A marked reduction in both GATA-3 mRNA and protein expression in HPV-immortalized cell lines was confirmed by reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry and was also shown to be apparent in cervical carcinoma cell lines. Immunohistochemical analysis of cervical tissue specimens showed a clear nuclear staining for GATA-3 in normal cervical squamous epithelium (n = 14) and all cervical intraepithelial neoplasia (CIN) I (n = 6) and CIN II lesions (n = 2). In contrast, 11% (1 of 9) of CIN III lesions and 67% (8 of 12) of cervical squamous cell carcinomas revealed a complete absence of GATA-3 immunostaining. Hence, complete down-regulation of GATA-3 expression represents a rather late event during cervical carcinogenesis. Whether GATA-3 down-regulation is etiologically involved in HPV-mediated immortalization and cervical carcinogenesis remains to be examined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Squamous Cell / pathology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Down-Regulation
  • Female
  • GATA3 Transcription Factor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Papillomaviridae*
  • RNA, Messenger / metabolism
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • RNA, Messenger
  • Trans-Activators