objective: transitional cell carcinoma (tcc) of the urinary bladder is the second common cancer of the genitourinary tract. several parameters such as clinical and pathological parameters, molecular factors, and etc play a role in determination of prognosis and type of treatment. in this research study, the relationship between grade and mdm2 oncoprotein overexpression in tcc of bladder was eva...

The tumour suppressor p53 is frequently mutated in tumours. Mutant p53 (Mutp53) proteins often gain new activities in promoting tumorigenesis, defined as gain-of-function (GOF). Mutp53 can accumulate to high levels in tumours, which promotes mutp53 GOF in tumorigenesis. The mechanism of mutp53 accumulation is poorly understood. Here we find that MDM2 isoforms promote mutp53 accumulation in tumo...

MDM2 is an oncoprotein that controls tumorigenesis through both p53-dependent and -independent mechanisms. Mdm2 mRNA level is transcriptionally regulated by p53 in response to stress such as DNA damage, and its protein level and subcellular localization are post-translationally modulated by the AKT serine/threonine kinase. Previous studies showed that PTEN, a dual specificity phosphatase that a...

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin‑ligase activity. MDM4 cooperates with MDM2‑mediated degradation, directly inhibiting transcription by binding to its transactivation domain. Our previous study reported the simultaneous inhibition of MDM2 and using nutlin‑3 (an inhibitor MDM2‑p53 interaction) chimeric small interfering RNA DNA‑sub...

Nilotinib is a selective BCR-ABL tyrosine kinase inhibitor related to imatinib that is more potent than imatinib. Nilotinib is widely used to treat chronic myelogenous leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The present study identifies Mouse double minute 2 homolog (MDM2) as a target of nilotinib. In studying ALL cell lines, we found that the expressi...

BACKGROUND MDM2 is a negative regulator of p53 and is upregulated in numerous human cancers. While different MDM2 splice variants have been observed in both normal tissues and malignant cells, their functions are poorly understood. METHODS We evaluated the effect of MDM2 splice variants by overexpression in MCF-7 cells and analyses of expression of downstream genes (qPCR and Western blot), su...

Genetic evidence has implicated both Mdm2 and MdmX as essential in negative regulation of p53. However, the exact role of MdmX in this Mdm2-dependent protein degradation is not well understood. Most, if not all, previous Mdm2 studies used GST-Mdm2 fusion proteins in the in vitro assays. Here, we show that the p53 polyubiquitination activity of GST-Mdm2 is conferred by the GST tag and non-GST-ta...

The MDM2 oncogene has both p53-dependent and p53-independent activities. We have previously reported that antisense MDM2 inhibitors have significant anti-tumor activity in multiple human cancer models with various p53 statuses (Zhang, Z., Li, M., Wang, H., Agrawal, S., and Zhang, R. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 11636-11641). We have also provided evidence that MDM2 has a direct r...

The protein MDM2 coded by the human homologue of mouse double minute-2 (mdm2) gene frequently overexpresses in malignant human breast and other tumors. Artificial amplification of mouse mdm2 gene derived from a transformed murine cell line enhances tumorigenic potential of murine cells. These evidences suggest oncogenic properties of human or mouse MDM2. The tumorigenic property of MDM2 is not ...

Mdm2 is the main regulator of p53 and is amplified in approximately 7% of all human cancers. MDM2 gene amplification as well as expression has been correlated to an increased tumorigenic potential. We have analyzed the prevalence of MDM2 gene amplifications and SNP309 in 284 colorectal tumors using a relatively new highly sensitive PCR/ligase detection reaction method in relation to TP53 mutati...