TY - JOUR
T1 - Down-regulation of GATA-3 expression during human papillomavirus-mediated immortalization and cervical carcinogenesis
AU - Steenbergen, Renske D.M.
AU - OudeEngberink, Vanessa E.
AU - Kramer, Debbie
AU - Schrijnemakers, Henri F.J.
AU - Verheijen, Rene H.M.
AU - Meijer, Chris J.L.M.
AU - Snijders, Peter J.F.
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036080870&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0002-9440(10)61143-1
DO - https://doi.org/10.1016/S0002-9440(10)61143-1
M3 - Article
C2 - 12057898
SN - 0002-9440
VL - 160
SP - 1945
EP - 1951
JO - American journal of pathology
JF - American journal of pathology
IS - 6
ER -