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

• Published in: Oncogene Vol. 14; no. 18; pp. 2149 - 2157
• Main Authors: SIMPSON, S, WOODWORTH, C. D, DIPAOLO, J. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 08.05.1997; Nature Publishing Group
• Subjects: Biological and medical sciences; Blotting, Northern; Cancer; Carcinogenesis; Carcinoma - genetics; Carcinoma - pathology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Cervical cancer; Cervical carcinoma; Cervix; Cervix Uteri - cytology; Cervix Uteri - physiology; Cervix Uteri - virology; Chromosomes, Human, Pair 21; DNA Methylation; DNA-Binding Proteins - genetics; Early Growth Response Protein 1; Epidemiology; Epithelium - pathology; Epithelium - virology; Female; Fundamental and applied biological sciences. Psychology; Gel electrophoresis; Gene Expression Regulation, Neoplastic; Human papillomavirus; Humans; Immediate-Early Proteins; Molecular and cellular biology; 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; Ribonucleic acid; RNA; Trans-Activators - genetics; Transcription factors; Transcription Factors - genetics; Transcriptional Regulator ERG; Translocation; Translocation, Genetic; Tumor cell lines; Tumor Cells, Cultured; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Chromosomal aberration; Human; Papovaviridae; Cell immortalization; Gene expression; Female genital diseases; Papillomavirus; Virus; Human papillomavirus 16; Cell line; Gene; Uterus; C-Onc gene; Uterine diseases; Abnormal chromosome; Abnormal chromosome G21; Tumor; Transcription factor
• ISSN: 0950-9232; 1476-5594
• 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.