G. Mariatos et al., Absence of mutations in the functional domains of the human MDM2 oncogene in non-small cell lung carcinomas, MUT RES-F M, 456(1-2), 2000, pp. 59-63
Citations number
34
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Increasing evidence suggests that MDM2 oncoprotein participates in a comple
x array of interactions with a plethora of molecules, including cell-cycle
and transcriptional regulators, as well as determinants of the cell differe
ntiation and senescence. The tumorigenic potential of MDM2 is mainly determ
ined by overexpression due to gene amplification, mRNA overexpression and p
ossibly translational enhancement. Although artificially created mutations
have been demonstrated to abolish normal MDM2 function, there is little inf
ormation concerning its mutational status in human tissues. In this study,
we screened all the functional domains of MDM2 for mutations in a series of
58 non-small cell lung carcinomas (NSCLCs), but none was found. Therefore,
we report that MDM2 mutations are an extremely rare phenomenon of non-smal
l cell lung carcinogenesis. A putative explanation for this observation may
be the labyrinth of interactions necessary for cell viability, in which MD
M2 takes part, a finding also supported by its stringent interspecies conse
rvation. (C) 2000 Elsevier Science B.V. All rights reserved.