Discrimination of oncogenic growth signals from normal growth signals is crucial for tumor suppression. The transcription factor E2F, the main target of pRB, plays central role in cell proliferation by activating growth‐promoting genes. E2F also plays an important role in tumor suppression by activating growth‐suppressive genes such as pro‐apoptotic genes. The regulatory mechanism of the latter genes is not known in detail, especially in response to normal and oncogenic growth signals. E2F is physiologically activated by growth stimulation through phosphorylation of pRB. In contrast, upon dysfunction of pRB, a major oncogenic change, E2F is activated out of control by pRB, generating deregulated E2F activity. We show here that the tumor suppressor TAp73 gene, which can induce apoptosis independently of p53, responds to deregulated E2F activity, but not to physiological E2F activity induced by growth stimulation in human normal fibroblasts. We identified E2F‐responsive elements (ERE73s) in TAp73 promoter that can specifically sense deregulated E2F activity. Moreover, RB1‐deficient cancer cell lines harbored deregulated E2F activity that activated ERE73s and the TAp73 gene, which were suppressed by re‐introduction of pRB. These results underscore the important role of deregulated E2F in activation of the TAp73 gene, a component of major intrinsic tumor suppressor pathways.
We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis co ... more
Flavonoids have well‐known antioxidant, anti‐inflammatory, and anti‐cancer activities. Isoflavone genistein is considered a potent antioxidant agent against oxidative stress. Although several mechanisms have been proposed, a clear antioxidant mechanism of genistein is still remain ... more
People can get oral cancers from UV (290‐400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV‐emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to or ... more
A new study from the University of Southern California (USC) has found a link between recreational marijuana use and an increased risk of developing subtypes of testicular cancer that tend to carry a somewhat worse prognosis. Published in CANCER the findings suggest that the potential cance ... more
Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient’s own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also ... more
The journal Stem Cells has announced Dr. Cinzia Rota as the winner of the annual Stem Cells Young Investigator Award. Co-sponsored by the International Stem Cell Symposium, the $10,000 prize is annually given to a young scientist who is the principal author of a research paper published in ... more