Our study was designed to explore the impact of MDM2 overexpression on the levels of various cell cycle regulatory proteins including Aurora kinase-B (AURK-B), CDC25C and CDK1, which are known to promote tumor progression and increase metastatic potential.
More than 50% mutations in human cancers along with the increase in expression of murine double minute 2 gene (mdm2), has been found as one of the reason for cancer progression.
Collectively, these data uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria that play critical roles in skeletal muscle physiology and may contribute to tumor progression.
Our findings suggest that MDM2 inhibitors could reduce cancer progression in part by reducing the pro-inflammatory environment created by senescent cells.
The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear.
A requirement for Mouse Double Minute 2 (MDM2) oncogene activation has been suggested to be associated with cancer progression and metastasis, including breast cancer.
RMS-YM may be useful for studies of the molecular pathways of tumorigenesis and tumor progression in rhabdomyosarcoma and for in vitro evaluation of newly developed therapeutic agents that target MDM2 or FRS2.
The MDM2-p53 feedback loop plays an important role in tumor progression and thus, increased understanding of the pathway has the potential to improve clinical outcomes for cancer patients.
Therefore, the binding of Mdm2 to the Slug mRNA appears to provide a novel mechanism through which Mdm2 promotes tumor progression in a manner independent of the presence of p53.
The data from the current study provide the first evidence that hdm2 mRNA is frequently mutated by alternative splicing in colorectal cancer, and may play a role in colorectal tumorigenesis or cancer progression.
We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.
Identification of Hdm2 as a downstream target of TGF-beta1 represents a critical prosurvival mechanism in cancer progression and provides another point for therapeutic intervention in late-stage cancer.
Inactivation of p53, by mutations and/or overexpression of the mdm2 gene, confers a selective advantage to tumor cells under hypoxic microenvironment during tumor progression.
Previous studies indicate that some tumors express alternatively or aberrantly spliced Mdm2 variants that are unable to bind p53, but whether these actively contribute to carcinogenesis or are a byproduct of cancer progression has been unclear.
These results suggest that the distribution of MDM2 reflects its nuclear-cytoplasmic shuttling ability; that interaction between p53 and MDM2 for tumor progression is not enhanced by point mutations at codon 17; and that the expression of MDM2 splice variants is a reason for the lack of its overexpression.
Although heparanase activity seems to play an essential role in tumor progression, expression of oncogenes, such as erbB2 and Mdm2 seems to play the dominant role in the development of ovarian cancer.
These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.
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.
In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.