Study published in JCI observed that TGF-beta-1 increased expression of the protein, which decreased p53 activity.

A group of researchers at Indiana University School of Medicine, Indianapolis, have figured out why the protein Mdm2 is overexpressed in late-stage breast cancers that have spread to other parts of the body. Their research revealed that Mdm2 helps cancer cells become more aggressive.

A large proportion of advanced, metastatic breast cancers are characterized by overexpression of Mdm2. The cause for this, however, has been unclear. A study titled “TGF-beta-1 induced expression of human Mdm2 correlates with late-stage metastatic breast cancer” appearing in The Journal of Clinical Investigation reveals some details in this process.

The Indiana University team found that a signaling pathway triggered by the molecule TGF-beta-1 increased Mdm2 expression in human cancer cell lines. Expression of activated molecules involved in this pathway correlated with Mdm2 expression in many late-stage breast cancer samples analyzed.

The increased level of Mdm2 in the human cancer cell lines led to decreased expression of the key tumor suppressor p53. More importantly, it enabled the cells to gain the ability to move freely in vitro after exposure to TGF-beta-1, which is a key feature of cells that cause metastatic tumors.

The investigators also observed that an antagonist of Mdm2 prevented TGF-beta-1 from enabling cells to move freely in culture. They thus suggest that targeting Mdm2 might help prevent progression of late-stage breast cancer.

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