title: Down-regulation of GATA-3 expression during human papillomavirus-mediated immortalization and cervical carcinogenesis.
abstract: 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.
authors.affiliation: Department of Pathology, Unit of Molecular Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Renske D M
authors.initials: RD
authors.lastname: Steenbergen
authors.forename: Vanessa E
authors.initials: VE
authors.lastname: OudeEngberink
authors.forename: Debbie
authors.initials: D
authors.lastname: Kramer
authors.forename: Henri F J
authors.initials: HF
authors.lastname: Schrijnemakers
authors.forename: Rene H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D050990:GATA3 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators