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Journal of Dental Research
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Biological

Characterization of Fibroblasts with Son of Sevenless-1 Mutation

E.J. Lee1, S.I. Jang1, D. Pallos2, J. Kather2 and T.C. Hart1,*

1 Human Craniofacial Genetics Section, NIDCR, National Institutes of Health, DHHS, Building 10, Room 5-2523, 10 Center Drive, Bethesda, MD 20892, USA; and
2 Department of Periodontology, University of Taubate, Brazil

Correspondence: * corresponding author, thart{at}mail.nih.gov

Although non-syndromic hereditary gingival fibromatosis (HGF) is genetically heterogeneous, etiologic mutations have been identified only in the Son of Sevenless-1 gene (SOS1). To test evidence of increased cell proliferation, we studied histological, morphological, and proliferation characteristics in monolayer and three-dimensional cultures of fibroblasts with the SOS1 g.126,142–126,143insC mutation. Histological assessment of HGF gingiva indicated increased numbers of fibroblasts (30%) and increased collagen (10%). Cell proliferation studies demonstrated increased growth rates and 5-bromo-2-deoxyuridine incorporation for HGF fibroblasts. Flow cytometry showed greater proportions of HGF fibroblasts in the G2/M phase. Attachment of HGF fibroblasts to different extracellular matrix surfaces demonstrated increased formation of protrusions with lamellipodia. HGF fibroblasts in three-dimensional culture showed greater cell proliferation, higher cell density, and alteration of surrounding collagen matrix. These findings revealed that increased fibroblast numbers and collagen matrix changes are associated with mutation of the SOS1 gene in vitro and in vivo.

Key Words: hereditary gingival fibromatosis • Son of Sevenless-1 • fibroblast • collagen

Journal of Dental Research, Vol. 85, No. 11, 1050-1055 (2006)
DOI: 10.1177/154405910608501115
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S.-I. Jang, E.-J. Lee, P. S. Hart, M. Ramaswami, D. Pallos, and T. C. Hart
Germ Line Gain of Function with SOS1 Mutation in Hereditary Gingival Fibromatosis
J. Biol. Chem., July 13, 2007; 282(28): 20245 - 20255.
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