Alterations of ΔTA‐p 73 splice transcripts during melanoma development and progression

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Abstract
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 (ΔTA‐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 ΔTA‐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 ΔTA‐p73 expression using isoform‐specific real‐time RT‐PCR. Based on our results, p73Δex2 and Δex2/3 spliced transcripts derived from the first promoter were significantly up‐regulated in melanoma metastases, whereas ΔN‐p73 generated from the second promoter was the predominant isoform in benign nevi. Moreover, increased expression of p73Δex2 and p73Δex2/3 correlated with high‐levels of both TA‐p73 and E2F1. Our data suggest a potential function of ΔTA‐p73 splice isoforms in melanoma progression.
Funding Information
  • Deutsche Krebshilfe (10-1934-Pü3)
  • University of Essen (107-05820/IFORES)