Researchers have known for a decade that the p53 tumor suppressor gene is important for killing cells as they proliferate under low-oxygen conditions inside tumors. As tumors grow they outstrip their oxygen supply. If a cell has a normal p53 gene, the p53 protein will eliminate cancerous cells, keeping tumor growth at bay. Under conditions of stress to the cell – such as radiation or chemotherapy and hypoxia – p53 normally eliminates tumors.
Composite of action of Buip3L and p53 under hypoxia.
Hypoxia, however, induces p53 to mutate: The less oxygen, the more mutations in the p53 gene, so cancer cells are not killed; instead, they proliferate. A team led by Wafik El-Deiry, MD, PhD, Associate Professor, Departments of Medicine, Genetics, and Pharmacology with the Abramson Cancer Center of the University of Pennsylvania, discovered a gene related to p53 called Bnip3L that can also cause cell death. The gene is turned on by p53 and a second transcription factor called hypoxia inducible factor, or HIF. The team silenced Bnip3L in cells with normal p53 and exposed cells to low oxygen conditions. In cell culture and in an animal model with implanted tumor cells, the researchers showed that tumors with silenced Bnip3L grew more aggressively in low oxygen conditions than cells and tumors with intact Bnip3L. El-Deiry and first author Peiwen Fei, MD, PhD, a post-doctoral fellow, report their findings in the December issue of Cancer Cell.
"From this, we predict in humans that another reason for tumor growth is the silencing of Bnip3L," says El-Deiry. "We think one of the ways that p53 suppresses tumors at their earliest stages is by turning on Bnip3L, and thats new. There is no information at present about how p53 works in the earliest stages of tumor growth, especially as the growth begins to outstrip the supply of nutrients and oxygen."
Karen Kreeger | EurekAlert!
Molecular doorstop could be key to new tuberculosis drugs
20.03.2018 | Rockefeller University
Modified biomaterials self-assemble on temperature cues
20.03.2018 | Duke University
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
20.03.2018 | Agricultural and Forestry Science
20.03.2018 | Life Sciences
20.03.2018 | Life Sciences