March 15, 2005
Epstein-Barr Virus Protein Crucial
To Its Role
In Blood Cancers
(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine have identified
a link between a critical cancer pathway and an Epstein-Barr
Virus (EBV) protein known to be expressed in a number
of EBV-associated cancers. Their findings demonstrate
a new mechanism by which EBV transforms human B cells
from the immune system into cancerous cells, which can
lead to development of B-cell lymphomas.
Erle S. Robertson, PhD, Associate Professor
of Microbiology and Director of Tumor Virology, with
Penn’s Abramson Cancer Center and
MD/PhD student Jason Knight, published
their results in the early March issue of Molecular
and Cellular Biology.
Using human cell cultures infected with the Epstein-Barr
virus, the investigators found that a specific viral
protein targets a molecule that normally regulates the
cell-cycle progression, or duplication process, of resting
B cells. In the presence of this viral protein - called
EBNA3C (for EBV nuclear antigen) - the cell cycle of
the usually quiescent human B cells gets a jump start,
which ultimately initiates uncontrolled growth.
EBV, a member of the herpesvirus family and one of the
most common human viruses, plays a role in cancers such
as lymphoproliferative diseases in transplant or AIDS
patients, Burkitt’s lymphoma, Hodgkin’s
lymphoma, and nasopharyngeal carcinoma, and also causes
the well-known disease, infectious mononucleosis. As
many as 95 percent of adults 20 years and older have
been infected with EBV, but show no symptoms.
“Viruses that are associated with cancers typically
target the cell cycle to gain control,” says Robertson.
“However, this is the first time that laboratory
research into how EBV drives the cancer process has
directly identified a critical component of the cell
cycle for control. Now we can develop targeted therapeutics
to disrupt the function of this viral protein.”
The researchers surmise that the first use of future
therapies from these studies will be in lymphoproliferative
disease in transplant and immunocompromised patients
because this is a clear case of EBV-driven B-cell lymphoma.
The use of peptides to block the interaction between
this essential EBV protein and the specific pathway
in human B cells is currently underway. Initial studies
show that the growth of EBV-associated cancer cells
can be inhibited in tissue-culture assays. The investigators
are actively pursuing this line of investigation for
developing potential therapies.
This research was funded by the National Institutes
of Health and the Leukemia and Lymophoma Society of
America. Nikhil Sharma, a student from Cherokee High
School, New Jersey who volunteers at Penn, was also
a co-investigator in this study.
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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
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.
Penn Health System is comprised of: its flagship
hospital, the Hospital of the University of Pennsylvania,
consistently rated one of the nation’s “Honor
Roll” hospitals by U.S. News & World Report;
Pennsylvania Hospital, the nation's first hospital;
Presbyterian Medical Center; a faculty practice plan;
a primary-care provider network; two multispecialty
satellite facilities; and home health care and hospice.