Role in Disease
Very commonly, cancer is associated with a loss of function of INK4a, ARF, Rb, or p53. Without INK4a, Cdk4/6 can inappropriately phosphorylate Rb, leading to increased E2F-dependent transcription. Without ARF, Mdm2 can inappropriately inhibit p53, leading to increased cell survival.
The tumor suppressor p53 is mutated in more than 50% of human cancers, and HDM2 is overexpressed in 5-10% of tumors. The INK4a/ARF locus is found to be deleted or silenced in many kinds of tumors. For example, of the 100 primary breast carcinomas, approximately 41% have p14ARF defects. In a separate study, 32% of colorectal adenomas (non-cancerous tumors) were found to have p14ARF inactivation due to hypermethylation of the promoter. Mouse models lacking p19Arf, p53, and Mdm2 are more prone to tumor development than mice without Mdm2 and p53, alone. This suggests that p19Arf has Mdm2- and p53-independent effects, as well. Investigating this idea lead to the recent discovery of smARF.
Read more about this topic: ARF Tumor Suppressor
Famous quotes containing the words role in, role and/or disease:
“Always and everywhere children take an active role in the construction and acquisition of learning and understanding. To learn is a satisfying experience, but also, as the psychologist Nelson Goodman tells us, to understand is to experience desire, drama, and conquest.”
—Carolyn Edwards (20th century)
“Nothing is ever simple. What do you do when you discover you like parts of the role you’re trying to escape?”
—Marilyn French (b. 1929)
“Hastiness and superficiality are the psychic diseases of the twentieth century, and more than anywhere else this disease is reflected in the press.”
—Alexander Solzhenitsyn (b. 1918)