Down-Regulation of GATA-3 Expression during Human Papillomavirus-Mediated Immortalization and Cervical Carcinogenesis

Autor: Steenbergen, Renske D.M., OudeEngberink, Vanessa E., Kramer, Debbie, Schrijnemakers, Henri F.J., Verheijen, Rene H.M., Meijer, Chris J.L.M., Snijders, Peter J.F.
Zdroj: American Journal of Pathology; June 2002, Vol. 160 Issue: 6 p1945-1951, 7p
Abstrakt: 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.
Databáze: Supplemental Index