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. 2005 Aug 19;94(8):718–724. doi: 10.1111/j.1349-7006.2003.tb01508.x

A naturally occurring p73 mutation in a p73‐p53 double‐mutant lung cancer cell line encodes p73α protein with a dominant‐negative function

Huqun 1, Yoshiyuki Endo 1, Hong Xin 1, Mitsu Takahashi 1, Toshihiro Nukiwa 1, Koichi Hagiwara 2,✉
PMCID: PMC11160092  PMID: 12901798

Abstract

p73, a close homolog of p53 tumor suppressor, induces growth arrest and apoptosis. However, its role in cancers is controversial because of the rarity of p73 mutations, lack of tumors in p73‐knockout mice, and the presence of multiple isotypes, among which ΔN isotypes inhibit the function of TA isotypes. We analyzed three naturally occurring p73 mutants found in lung cancer cell lines, NCI‐H1155, DMS 92 and A427. NCI‐H1155 is a cell line that has a p73 mutation [p73(G264W)] in the DNA‐binding domain, as well as a p53 mutation [p53(R273H)], which is frequently found in human cancers and has a “gain‐of‐function” characteristic. p73α(G264W) not only lacks transactivation activity itself, but also suppressed the transactivation activity of the wild‐type p73α in a dose‐dependent manner, indicating that p73α(G264W) is a dominant‐negative mutant. p73α(G264W) failed to suppress colony formation. We tested two other mutations, p73(Del418) in DMS 92 and p73(Del603) in A427. Both mutants retained similar levels of transactivation activity and suppression of colony formation to those of wild‐type p73. The biological significance of these two mutations is unclear. In NCI‐H1155 cells the coexistence of mutations that abrogate the normal functions of p73 and p53 may indicate that each mutation confers an additive growth advantage upon the cells.

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