Not long ago, a current National Institute of Dental and Craniofacial Research scientist and his colleagues determined that people born with hereditary gingival fibromatosis, a rare condition in which their gums grow abnormally over their teeth, inherit an altered form of a gene called SOS1. The finding was particularly intriguing because SOS1 encodes a protein that is known to activate the ras pathway, one of the key growth signals in our cells. This suggested that the ras pathway was likely involved in normal and abnormal gingival growth, an idea that was previously unknown. As published online in the Journal of Biological Chemistry (May 17), the scientists have added important mechanistic details to explain their initial finding. Using primary gingival fibroblast cells, they determined that an abnormal, truncated version of the SOS1 protein can reach the cell membrane where, without interacting with growth factor stimuli, it causes sustained activation of the growth-regulating ras/MAPK pathway. With this key pathway stuck in the on position, the gingival fibroblasts had an increase in the expression of cell cycle-regulating proteins and gene-activating transcription factors. As the authors noted, these findings suggest a molecular cause of the abnormal proliferation of gingival fibroblasts and, with further elucidation, suggest a more defined area to target in hopes of halting gingival overgrowth in people with hereditary gingival fibromatosis.
(Source: Science News in Brief, NIDCR Web site, May 31, 2007)
