Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Reversal of role for a viral protein associated with the development of lymphoma

23.08.2005


Protein thought to promote lymphoma by merely preventing cancer cells from dying appears to actively promote cancer cell growth



A protein previously thought to merely hinder the activity of a key cellular protein linked to cancer cell death, now appears to mimic the cellular signaling of that protein; potentially leading to the development of lymphoma. The findings, published in the Aug. 22 online edition of Proceedings of the National Academy of Sciences (PNAS), demonstrate that a viral protein associated with human herpesvirus 8, or HHV8, may help to cause lymphoma by activating a key pathway involved in the production of lymphocytes, a common cell type found in lymphoid tissue that divide over and over and eventually develop into lymphoma.

The protein, called vFLIP K13, had been thought to protect virally infected cells from attack by the body’s own immune system by inhibiting the activity of a cellular protein called caspase 8 that is associated with apoptosis, or programmed cell death. However, when Preet M. Chaudhary, M.D., Ph.D., senior author of the study and professor of medicine at the University of Pittsburgh School of Medicine, and his colleagues analyzed transgenic mice expressing vFLIP K13, they found that vFLIP K13 failed to block cell death pathways and instead mimicked a recently discovered signaling function of caspase 8, which led to the proliferation of lymphocytes.


Dr. Chaudhary and his colleagues observed tumor formation in 59 mice over the course of 30 months. They found that the vFLIP-expressing transgenic mice had more lymphomas than the control group mice; 11.8 percent compared 1.8 percent, respectively.

"We were surprised to see that the mouse model we developed based on vFLIP K13 did not look like the other models in which caspase 8 function was inhibited," said Dr. Chaudhary. "It indicated to us that the main function of this protein is not to block caspase 8 activation."

Further analysis also revealed that instead of inhibiting caspase 8, vFLIP K13 copied its signaling activity resulting in the activation of a distinct cellular pathway called NF-?B that is involved in the development of lymphoma. "In effect, vFLIP K13 actively promoted the growth of cancer cells through this pathway. Based on these findings, we believe the NF-?B pathway may be a promising target for novel therapies directed against HHV8-associated tumors," said Dr. Chaudhary. He added that there is a dire need for new therapies that target this disease since most patients with HHV8-associated lymphomas are highly immune suppressed and are difficult to treat given the toxicity associated with conventional therapies.

In addition to its role in the development of HHV8-associated cancers, the NF-?B pathway also may be implicated in lymphomas that are not caused by HHV8. "There are potentially widespread applications of this finding and our next step will be to discover how involved this pathway is in the development of lymphomas that are not associated with HHV8," said Dr. Chaudhary.

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. They begin with the malignant transformation of a lymphocyte in the lymphatic system. The American Cancer Society estimates that 63,740 people in the U.S. will be newly diagnosed with lymphoma by the end of 2005.

HHV8, originally linked to Kaposi’s sarcoma –the most common cancer among AIDS patients – also is associated with lymphoid diseases such as primary effusion lymphoma and multicentric Castleman’s disease, a noncancerous but severe disorder characterized by enlargement of the lymph nodes. Recent studies have also linked HHV8 infection to HIV-related solid immunoblastic/plasmablastic lymphomas.

In addition to Dr. Chaudhary, authors on the study include Priti Chugh, Ph.D., Sunny Zachariah, M.S., Arvind Kumar, Ph.D., Alice L. Smith, M.D., and James A. Richardson, Ph.D., Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas; and Hittu Matta, Ph.D., and Sandra Schamus, B.S., Hillman Cancer Center, University of Pittsburgh Cancer Institute.

Clare Collins | EurekAlert!
Further information:
http://www.upmc.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>