Novel model of osteosarcoma

Jun 15, 2008

In the June 15th issue of G&D, Dr. Stuart Orkin (HHMI, Dana-Farber Cancer Institute, Children's Hospital Boston) and colleagues present a new mouse model of osteosarcoma.

Osteosarcoma is the most common type of malignant bone cancer, and one of the most lethal: The 5-year survival rate is only about 60%, and this statistic drops steeply once the cancer spreads. Osteosarcoma results from the dysregulated growth of osteoblasts (the cells that form the bone matrix). It primarily develops near the ends of the femur, tibia or humerus, and is usually diagnosed during adolescence, when the long bones of the body are undergoing rapid growth.

While the precise causes of osteosarcoma are unknown, it is evident that two tumor suppressor genes – p53 and Rb – are involved, as children with familial mutation syndromes affecting either of these genes have higher incidences of osteosarcoma.

Dr. Orkin's team has developed a novel experimental system to model the genetics of human osteosarcoma. The researchers generated a strain of transgenic mice lacking specifically the p53 and Rb genes in an early osteoblast progenitor cell population. All mutant animals rapidly developed osteosarcomas, with clinical, histo-cytological and molecular features closely recapitulating the human disease.

The scientists concluded that p53 loss is essential for the development of osteosarcoma, and that while Rb gene mutation acts synergistically with p53 loss to facilitate carcinogenesis, loss of Rb, alone, is not sufficient to induce osteosarcomagenesis.

Ultimately, this high-fidelity animal model will further elucidate the genetic contributions to osteosarcoma, and enable researchers to rationally design and test new therapies. Dr. Orkin is hopeful that "our work will stimulate translational efforts to develop novel therapies for this devastating bone tumor".

Source: Cold Spring Harbor Laboratory

Explore further: Crystal structure reveals how minor variations make receptor proteins activate or inhibit natural killer cells

add to favorites email to friend print save as pdf

Related Stories

Coal gas boom in China holds climate change risks

2 minutes ago

Deep in the hilly grasslands of remote Inner Mongolia, twin smoke stacks rise more than 200 feet into the sky, their steam and sulfur billowing over herds of sheep and cattle. Both day and night, the rumble ...

Fossil arthropod went on the hunt for its prey

27 minutes ago

A new species of carnivorous crustacean has been identified, which roamed the seas 435 million years ago, grasping its prey with spiny limbs before devouring it. The fossil is described and details of its lifestyle are published ...

Water crisis threatens thirsty Sao Paulo

8 hours ago

Sao Paulo is thirsty. A severe drought is hitting Brazil's largest city and thriving economic capital with no end in sight, threatening the municipal water supply to millions of people.

Canada to push Arctic claim in Europe

8 hours ago

Canada's top diplomat will discuss the Arctic with his Scandinavian counterparts in Denmark and Norway next week, it was announced Thursday, a trip that will raise suspicions in Russia.

Google to help boost Greece's tourism industry

8 hours ago

Internet giant Google will offer management courses to 3,000 tourism businesses on the island of Crete as part of an initiative to promote the sector in Greece, industry union Sete said on Thursday.

Recommended for you

User comments : 0