Increased expression of p73Deltaex2 transcript in uveal melanoma with loss of chromosome 1p.
The loss of chromosome 1p and chromosome 3 is associated with metastatic disease and decreased survival of uveal melanoma (UM) patients. The p53 homologues, p73 and p63, are located on chromosomes 1p and 3q, respectively. Both are able to activate p53 target genes, resulting in growth arrest, apoptosis and differentiation. N-terminally truncated isoforms of these genes may act as dominant negative inhibitors of wild-type p53 and transactivating activity. Although, p53 is frequently involved in several malignancies it does not play a major role in UM. Altered expression has been reported for both p63 and p73 in various malignancies. In this study, fluorescent in-situ hybridization was performed to identify gains or losses of p63 and p73 loci in UM. The expression of the different p63 and p73 isoforms was evaluated by reverse transcriptase PCR followed by Southern blot analysis. Furthermore, the expression pattern of the various DeltaTAp73 transcripts was analysed in seven primary UMs and 11 UM-derived cell lines using isoform-specific real-time PCR. Our results indicated that the isoform p73Deltaex2/3 was abundantly expressed and a relative loss of the p73 locus was associated with the upregulation of p73Deltaex2 and TAp73 transcripts. N-terminal transactivation forms of both p73 and p63 were observed in primary and metastasis-derived cell lines, as well as in primary melanomas, but in only one of the cell lines a DeltaNp63 mRNA transcript was observed. Our data suggest a potential function of p73 deletion transcripts in UM progression.
Kilic
Emine
E
Department of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands.
Brüggenwirth
Hennie T
HT
Meier
Marit
M
Naus
Nicole C
NC
Beverloo
H Berna
HB
Meijerink
Jules P
JP
Luyten
Gre P
GP
de Klein
Annelies
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation; D014604:Uveal Neoplasms / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins