We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression.
The amplification and overexpression of HDM2 plays a role in tumorigenesis via inactivation of p53-dependent cell cycle arrest. p14ARF, an alternate transcript of the INK4A tumor suppressor locus, prevents hdm2-induced transcriptional silencing of p53 by binding hdm2.
We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume.
Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.
If the oncoprotein is defective in growth arrest or if the cells are insensitive to MDM2 mediated growth arrest, premature progression of cell cycle may lead to tumorigenesis.
Our findings suggest that by inducing p65 expression, MDM2 has a p53-independent role in tumorigenesis, which may further elucidate the association between MDM2 overexpression and resistant disease in childhood ALL.
Gains and high-level amplifications of 12q14-q22, which were the most frequent genomic imbalances, partly reflected an MDM2 amplification, indicating the importance of this region in the tumorigenesis of sarcomas.
To elucidate the role of p53/p16(INK4a)/RB1 pathways in prostate carcinogenesis, we analyzed the p14(ARF), p16(INK4a), RB1, p21(Waf1), p27(Kip1), PTEN, p73, p53, and MDM2 gene status of multiple areas within 16 histologically heterogeneous prostate carcinomas using methylation-specific polymerase chain reaction, differential polymerase chain reaction, and immunohistochemistry.
Both the disorders of the p53/MDM2/p14(ARF) and the p16(INK4a)/RB signaling pathways have been found to play an essential role in tumorigenesis of various brain tumors.
Disruption of either the p14ARF- mdm2- p53 or p16INK4A- Rb1 pathways produces a breakdown of regulatory mechanisms and creates a gateway for tumorigenesis.
Our results imply that the current paradigm for understanding Mdm2 action during oncogenesis is incomplete, and its splice variants contribute to human cancer.
Inactivation of the p53 pathway, by gene mutation or by MDM2 overexpression, would enable cells to escape from cell cycle arrest and apoptosis and could contribute to tumorigenesis.
Multiple spliced forms of Mdm2 transcripts have been observed in human tumors; however, the contribution of these variant transcripts to tumorigenesis is unknown.
These results suggest that accumulation of MDM2 without gene amplification may be one of the major molecular events occurring in the tumorigenesis of PXA.
Elevated expression of p53, MDM2, and p14(ARF) in benign and malignant ameloblastomas suggests that alteration of the p53-MDM2-p14(ARF) cascade is involved in oncogenesis and/of malignant transformation of odontogenic epithelium. p53 gene status implied that p53 mutation might play a minor role in neoplastic changes of odontogenic epithelium.
New papers now provide evidence that levels of Mdm2 in humans or presence of mutant forms of p53 in mice can have profound impacts on survival and tumorigenesis.
The pRb (pRb/p16(INK4a)/cyclin D1) and p53 (p14(ARF)/mdm2/p53) pathways are the two main cell-cycle control pathways frequently targeted in tumorigenesis, and the alterations occurring in each pathway depend on the tumor type.