Alterations of DeltaTA-p 73 splice transcripts during melanoma development and progression.
In the last 2 years, it has become apparent that the p53-family members p53 and p73 play fundamentally different roles in human malignancies. In contrast to p53, many studies on cancer patients failed to detect mutational inactivation of p73 and reported overexpression of wild-type p73 instead. A possible explanation was provided by the recent discovery of N-terminal truncated isoforms of p73 (DeltaTA-p73) that act as dominant-negative inhibitors of wild-type p53 and TA-p73 and result in tumor growth in nude mice. We investigated the role of DeltaTA-p73 in the development and progression of human melanomas, which lack p53 mutations. We analyzed 8 benign melanocytic nevi, 8 primary melanomas and 19 melanoma metastases for alterations of TA-p73 and DeltaTA-p73 expression using isoform-specific real-time RT-PCR. Based on our results, p73Deltaex2 and Deltaex2/3 spliced transcripts derived from the first promoter were significantly up-regulated in melanoma metastases, whereas DeltaN-p73 generated from the second promoter was the predominant isoform in benign nevi. Moreover, increased expression of p73Deltaex2 and p73Deltaex2/3 correlated with high-levels of both TA-p73 and E2F1. Our data suggest a potential function of DeltaTA-p73 splice isoforms in melanoma progression.
Tuve
Sebastian
S
Center for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen Medical School, Essen, Germany.
Wagner
Stephan N
SN
Schittek
Birgit
B
Pützer
Brigitte M
BM
D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000556:secondary; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins