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NIH study confirms location of stem cells near cartilage-rich regions in bones
Date:4/26/2010

was Constantine A. Stratakis, M.D., D.Sc., acting director of the NICHD Division of Intramural Research. Other authors of the study were from the NICHD; the NIH's Division of Veterinary Resources and the National Institute of Dental and Craniofacial Research; as well as the Johns Hopkins University School of Medicine and The Ohio State University.

The researchers undertook the study to learn more about the role of two genes, dubbed Prkar1a and prkaca, in a key chemical sequence that provides energy to cells. Prkar1a has been implicated in a variety of rare human cancers, of the bone, nervous system, and thyroid. When the two genes are working normally, bone cell growth proceeds normally and cancerous overgrowth is kept in check. In previous research, the researchers learned that tumors formed in numerous tissues when they inactivated prkar1a.

In the current study, they inactivated one copy each of the two genes. Like human beings, mice have two copies of most genes. The mice in the study had one functioning copy each of prkar1a and prkaca and one non-functioning copy of each gene.

The researchers predicted that disabling only one copy of each gene would offer protection from bone tumor growth. In fact, the combination had the opposite effect. Tumorous growths were unexpectedly prolific and developed much earlier than expected: Tumors appeared in mice as young as 3 months old, compared with 6 to 9 months old in the previous studies, in which only prkar1a had been inactivated. Moreover, abnormal growths formed near cartilage in the legs, along the tail, and the remaining vertebrae of the mice.

The bone tumors were also more extensive in the mice with the two inactivated genes compared with their counterparts having only a single inactivated gene. All mice with the two mutations had abnormal growths on their tail bones by the time they were 9 months old and showed abnormalities in their vertebrae by 12 months.

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Contact: Robert Bock
bockr@mail.nih.gov
301-496-5133
NIH/National Institute of Child Health and Human Development
Source:Eurekalert

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