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 thi s disease, other factors are also involved, Altered expression of the sts family transcription factors erg and ets-2 was found associated wi th the development of cervical carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell line, CX16-2, which has HPV in tegrated at a translocation breakpoint t(19;21) involving 21q22.2-22.3 , where these genes have been mapped. Six of 10 cervical carcinoma cel l lines overexpressed ets-2 RNA suggesting an association of overexpre ssion with cervical cell neoplasia. A clonally related pair of cervica l 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 cer vical cells and C-4II, C-4II expressed a 5.3 kb erg transcript not see n in C-4I, ectocervical cells or other cervical carcinoma cell lines e xamined. Pulsed field gel electrophoresis was used to analyse changes in DNA fragments related to structural changes and to construct a phys ical map encompassing erg and ets-2. Alterations in erg and ets-2 RNA expression in each of three different cell lines examined were associa ted,vith translocations. Association between altered expression of erg and ets-2 and altered regional structural suggests that these genes a re important targets in cervical carcinogenesis.