Regulating p73 isoforms in human tumours


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Abstract

Although mutations in theTP73gene are extremely rare in human tumours, altered expression is common. In some tumours, most notably leukaemias and lymphomas, expression ofTP73is reduced, suggesting a tumour suppressor role. In contrast,TP73is over-expressed in many other tumour types, implying that it has oncogenic functions in human tumourigenesis. These conflicting scenarios can be reconciled by the observations that theTP73gene produces p53-like isoforms (TAp73) and anti-p53 isoforms (ΔTAp73). Thus, loss of TAp73 or over-expression of ΔTAp73 should each promote oncogenic transformation, and the balance of expression of the opposing isoforms is the crucial factor. The mechanisms that regulate expression of TP73 isoforms are therefore of great interest. Recent data provide evidence for interacting roles of ZEB1, p300, and a polymorphic 73 bp deletion in intron 1 of the humanTP73gene in this process. Importantly, alterations to the proposed regulatory pathway for controlling TP73 isoform expression in colorectal cancer are associated with adverse clinico-pathological characteristics. Because p73 is also associated with tumour chemosensitivity, these new findings should provide prognostic information and have the potential to guide future therapeutic decisions.

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