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.
MDM2 knockdown in p53 mutant NSCLC H2009 cells induced significant cell cycle arrest, apoptosis and growth inhibition through upregulation of p21 and activation of caspase-3.
In view of this dichotomy in its functions and its critical role in cell cycle control, this study examined the following four aspects of E2F-1 in a panel of 87 non-small cell lung carcinomas (NSCLCs), previously analysed for defects in the pRb-p53-MDM2 network: firstly, the status of E2F-1 at the protein, mRNA and DNA levels; secondly, its relationship with the kinetic parameters and genomic instability of the tumours; thirdly, its association with the status of its transcriptional co-activator CBP, downstream target PCNA and main cell cycle regulatory and E2F-1-interacting molecules pRb, p53 and MDM2; and fourthly, its impact on clinical outcome.
Moreover, Cox regression analysis showed that MDM2 mRNA expression was a significantly independent favorable prognostic factor in non-small-cell lung cancer (NSCLC) patients.
Surprisingly, HL001 selectively suppresses tumor growth in p53 wild-type NSCLC harboring Arg72 homozygous alleles (p53-72R) through disrupting interaction between MDM2 and p53-72R in a CypA-dependent manner.
In conclusion, present study demonstrated that MDM2 (309 T > G) polymorphism may be one of the important factors for the increased expression mdm2, which was associated with down-regulation of p53 at messenger RNA (mRNA) level and ultimately may contribute in the poor clinical outcome of the non-small cell lung cancer patients, thus may prove as a promising target for the treatment of non-small cell lung cancer at molecular level.
Alterations of the p16-pRb pathway and the chromosome locus 9p21-22 in non-small-cell lung carcinomas: relationship with p53 and MDM2 protein expression.
The aim of the present study was to investigate the influence of genetic variants of MDM2 on chemotherapy-related toxicities and clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC).
Furthermore, miR-34b downregulates Met, with subsequent changes of downstream p53 (phospho S392) and Mdm2, and inversely p53 upregulates miR-34b in a feedback loop, which provides new insights into the roles of miR-34 family members in the regulation of signaling pathways of NSCLC.
Our data suggest that immunopositivity of p14ARF together with a low expression of MDM2 contributes to accumulation of the wild-type p53, and that deregulation of the p53-MDM2-p14ARF pathway is important in the pathogenesis and outcome of a subset of NSCLC.
This study investigated whether the functional polymorphisms in P53 pathway genes, P53 Arg72Pro (rs1042522), P73 G4C14-to-A4T14 (rs2273953 and rs1801173), and MDM2T309G (rs2279744), alone or in combination, affect survival in advanced non-small cell lung cancer (NSCLC) patients.
We determine that MDM2 c.14 + 309T > G was significantly associated with severe hematologic and overall toxicities for advanced NSCLC patients treated with platinum-based chemotherapy, especially for patients aged 57 and younger.
To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials.
Here, we report the discovery of a molecular interaction between WDR79 and USP7 and show its functional significance in linking the Mdm2-p53 pathway to the proliferation of NSCLC cells.