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.
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.
Simpson
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S
Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Woodworth
C D
CD
DiPaolo
J A
JA
D015152:Blotting, Northern; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002584:Cervix Uteri / Q000166:cytology / Q000502:physiology / Q000821:virology; D002891:Chromosomes, Human, Pair 21; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D004848:Epithelium / Q000473:pathology / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C497325:EGR1 protein, human; C107465:ERF protein, human; C072312:ERG protein, human; C494069:ETS2 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; C059731:oncogene protein E7, Human papillomavirus type 16