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Study of hypoxia and new gene shows early-stage action of p53 tumor suppressor gene
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.
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 that's 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."
Understanding how cells die after they are starved for oxygen is important for fighting cancer as well as other diseases.
"Down the road we would like to find strategies to turn Bnip3L back on to restore the ability to die under hypoxia now that
we know how it happens in the first place," says El-Deiry.
This work was funded by the Howard Hughes Medical Institute and by grants from the National Institutes of Health. This
release and associated images can be found at: http://www.uphs.upenn.edu/news.
The Abramson Cancer Center of the University of Pennsylvania was established in 1973 as a center of excellence in cancer
research, patient care, education and outreach. Today, the Abramson Cancer Center ranks as one of the nation's best in cancer
care, according to U.S. News & World Report, and is one of the top five in National Cancer Institute (NCI) funding. It is one
of only 39 NCI-designated comprehensive cancer centers in the United States. Home to one of the largest clinical and research
programs in the world, the Abramson Cancer Center of the University of Pennsylvania has 275 active cancer researchers and 250
Penn physicians involved in cancer prevention, diagnosis and treatment.
PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as
the nation's first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation's first
integrated academic health system).
Penn's School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S.
News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700
students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of
physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three owned hospitals [Hospital of the University of Pennsylvania,
which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania
Hospital, the nation's first hospital; and Presbyterian Medical Center]; a faculty practice plan; a primary-care provider
network; two multispecialty satellite facilities; and home care and hospice.
Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-662-2560
University of Pennsylvania Medical Center
Studiul de hipoxie ºi noi de gene de la începutul show-etapã de acþiune de p53 tumoare suppressor gene - Study of hypoxia and new gene shows early-stage action of p53 tumor suppressor gene - articole medicale engleza - startsanatate