Regulation of p53 isoform expression in renal cell carcinoma.
Differential expression of p53 isoforms might participate in the marked resistance towards conventional chemotherapy of renal cell carcinomas (RCCs). Therefore, we analysed their differential expression and regulation in RCCs. RCCs expressed a more p53 activating isoform pattern during tumor initiation and progression, in vivo. In vitro, two cell lines exhibiting a similar sensitivity towards Topotecan-induced cell death revealed a similar induction of p53 target genes but strongly differed in their extent of apoptosis. Furthermore, they strongly differed in their basal expression patterns and differential regulation of the isoforms. In conclusion, our study examined for the first time the differential expression and regulation of all p53 isoforms in a tumor in vivo. Furthermore, novel results in our in vitro studies show that p53 isoforms are strongly differentially regulated by chemotherapy in RCCs and that expression and regulation of so-called "p53-target genes" are obviously at least in part regulated by other transcription factors. In addition, our original findings show that p53 isoform expression in RCC cell lines is of minor importance for sensitivity towards chemotherapy.
Institute of Pathology, Heinrich-Heine University Hospital, 40225 Duesseldorf, Germany.
Linda
L
van den Berg
Adebowale Daniel
AD
Segun
Sabrina
S
Mersch
Nina
N
Blasberg
Edgar
E
Grinstein
Daniel
D
Wai
Martin
M
Anlauf
Helmut Erich
HE
Gabbert
Csaba
C
Mahotka
Sebastian
S
Heikaus
D001483:Base Sequence; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53