What causes MDM2 amplification?
MDM2 amplification has been detected in many human malignancies, including lung cancer, colon cancer and other malignancies. MDM2 overexpression is associated with chemotherapeutic resistance in human malignancies.
What does MDM2 amplification mean?
MDM2 amplification by FISH is designed to detect amplification of the MDM2 gene to aid in patient diagnosis of soft tissue and bone tumors. In soft tissue tumors, MDM2 amplification is a frequent and specific finding in well differentiated liposarcoma/atypical lipomatous tumor (ref.
How does MDM2 regulate p53?
MDM2 negatively regulates p53 by targeting the ubiquitin ligase activity of MDM2. A complementary approach to prevent p53 degradation by MDM2 is to develop agents designed to inhibit the E3 ligase activity of MDM2 directly so as to mimic the effects of ARF or the ribosomal protein L11.
What does MDM2 positive mean?
A positive result is consistent with amplification of the MDM2 gene locus (12q15) and supports the diagnosis of parosteal osteosarcoma or low-grade central osteosarcoma. A negative result indicates an absence of amplification of the MDM2 gene locus (12q15).
Is MDM2 a tumor suppressor gene?
The key target of Mdm2 is the p53 tumor suppressor. Mdm2 has been identified as a p53 interacting protein that represses p53 transcriptional activity. Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53.
Does p53 bind to MDM2?
MDM2 directly binds to the transactivation domain of p53 and inhibits its transcriptional activity, causes the ubiquitination and proteasomal degradation of p53, and exports p53 out of the nucleus which promotes p53 degradation and inhibits its activity.
What kind of protein is MDM2?
Using immunoprecipitation experiments with U937 cell lysates (leukemia cells), MDM2 was identified as an RB-binding protein. RB is a potent tumor suppressor that is mutated in different kinds of cancers. MDM2 inhibits the ability of RB to inhibit E2F1 function, thus inhibiting arrest of the cell cycle in G1 (69, 70).
Is MDM2 a bona fide human oncogene?
The role of MDM2 as a bona fide human oncogene was cemented when it was discovered to be genetically amplified in more than a third of human sarcoma samples (Oliner et al. 1992). Subsequent studies revealed MDM2 amplification in a range of tumor types outside of sarcoma (Momand et al. 1998).
How can Mdm2 be up-regulated?
Although MDM2 amplification is one important means by which MDM2 expression can be up-regulated, other mechanisms for overexpressing MDM2 have been proposed. One such mechanism that has received significant attention involves germline inheritance of a SNP, SNP309, in the first intron of the MDM2 promoter (Bond et al. 2004).
What is functionally relevant Mdm2 amplification?
Functionally relevant MDM2 amplification was defined as the CN above which MDM2 amplification and p53 mutation were mutually exclusive (dashed line at MDM2 log2CN ratio ≥2.25 in Aand B). View this table: In this window In a new window
Does MDM2 gene amplification affect tumor progression in differentiated adipose-tissue tumors?
MDM2 gene amplification in bone and soft-tissue tumors: Association with tumor progression in differentiated adipose-tissue tumors. Int J Cancer64: 342–346. CrossRefMedlineWeb of ScienceGoogle Scholar OhmiyaN, TaguchiA,