Altered expression of Erg and Ets-2 transcription factors is associated with genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines

Oncogene. 1997 May 8;14(18):2149-57. doi: 10.1038/sj.onc.1201058.


Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in cervical cancer. Although epidemiologic and experimental evidence indicates a prominent role for HPV infection in the development of this disease, other factors are also involved. Altered expression of the ets family transcription factors erg and ets-2 was found associated with the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical carcinoma cell lines overexpressed ets-2 RNA suggesting an association of overexpression with cervical cell neoplasia. A clonally related pair of cervical carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II. C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associated with translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes are important targets in cervical carcinogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Blotting, Northern
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic
  • Cervix Uteri / cytology
  • Cervix Uteri / physiology
  • Cervix Uteri / virology
  • Chromosomes, Human, Pair 21*
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Epithelium / pathology
  • Epithelium / virology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immediate-Early Proteins*
  • Oncogene Proteins, Viral / genetics
  • Papillomavirus E7 Proteins
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / genetics*
  • Repressor Proteins*
  • Restriction Mapping
  • Retroviridae Proteins, Oncogenic / genetics
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*
  • Transcriptional Regulator ERG
  • Translocation, Genetic
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology


  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • EGR1 protein, human
  • ERF protein, human
  • ERG protein, human
  • ETS2 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Retroviridae Proteins, Oncogenic
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Regulator ERG
  • oncogene protein E7, Human papillomavirus type 16