Absence of mutations in the functional domains of the human MDM2 oncogene in non-small cell lung carcinomas

Citation
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
ISSN journal
13861964 → ACNP
Volume
456
Issue
1-2
Year of publication
2000
Pages
59 - 63
Database
ISI
SICI code
1386-1964(20001130)456:1-2<59:AOMITF>2.0.ZU;2-3
Abstract
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.