The results suggest that aberrant Mdm2 and p53 phenotypes are frequent events in bladder cancer and may be involved in tumorigenesis or tumor progression in urothelial neoplasias.
Mutation may lead to nuclear accumulation of p53 protein; however, inactivation of p53 by nuclear exclusion and interaction with the mdm2 protein also appear to be important in tumorigenesis.
Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) accumulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene product; and c) p53 and mdm-2 are more important in late events in melanoma carcinogenesis.
Since p53 mutations, MDM2 overexpression, and HPV infection are all considered to abrogate the normal function of p53 protein, each of these genetic changes may be equally important in tumorigenesis.
Because altered expression of the p53 tumor suppressor gene and the mdm2 proto-oncogene have been demonstrated in a wide variety of tumors, we carried out studies to assess the possible involvement of these two genes in meningioma tumorigenesis.
Our results suggest that MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2 protein overexpression might represent an alternative mechanism by which p53 is inactivated in the early stages of laryngeal cancer tumorigenesis.
Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function.
Thus, MDM2 may confer TGF-beta resistance in a subset of tumors and may promote tumorigenesis by interference with two independent tumor suppressors, p53 and Rb.
Obviously MDM2 amplification and LOH at the Rh and p53 genes do not occur simultaneously in the oncogenesis of liposarcomas, as is the case for MDM2 amplification and p53 gene mutations (with one exception).
The transgenic mice are predisposed to spontaneous tumor formation, and the incidence of sarcomas observed in the Mdm2-transgenic mice in the presence or absence of functional p53 demonstrates that, in addition to Mdm2-mediated inactivation of p53, there exists a p53-independent role for Mdm2 in tumorigenesis.
The aim of this study was to determine whether alternative splicing of MDM2 occurs during breast tumorigenesis in mice and humans and whether protein coding sequences were affected.
Overexpression of Mdm2 in cancer cells with otherwise wild-type p53 is believed to be an alternative mechanism for p53 inactivation during carcinogenesis.
The aim of this report was to assess p53 and MDM2 expression in odontogenic cysts and tumours, as they are known to play important roles in cell proliferation and tumorigenesis.
It is tempting to speculate that ICGTs might have the same cellular origins as TGTs with abnormalities in p53 and mdm2, which could play an important role of tumorigenesis.
These results suggest that the amplification and/or overexpression of mdm2 may be one of the major molecular events occurring in the tumorigenesis of ependymomas.
The differential compartmentalization of the three isoforms of MDM2 suggests that each has a distinct function, potentially in the regulation of p53 and other gene products implicated in oral tumorigenesis.
Our results show that MDM2 predisposes to tumorigenesis when expressed at an early stage of differentiation, and provide a mouse model of MDM2 tumorigenesis relevant to p53's tumour suppressor functions.
These results suggest that MDM2 overexpression is an early event in oral carcinogenesis through the functional inactivation of the wild-type p53, and corresponding alterations of MDM2 and p53 contribute to the oral carcinogenesis.
The human MDM2 oncogene, well known as the tumor suppressor gene p53's partner, plays an important role in tumorigenesis whether it is dependent on or independent of TP53.