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Upregulation of c‐Fos protooncogene expression in pagetic osteoclasts
Author(s) -
Hoyland Judith,
Sharpe Paul T.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090808
Subject(s) - immunohistochemistry , paget's disease of bone , bone resorption , osteosarcoma , genetically modified mouse , transgene , pathology , downregulation and upregulation , phenotype , in situ hybridization , resorption , osteoblast , gene expression , oncogene , gene , biology , cancer research , endocrinology , in vitro , medicine , disease , genetics , cell cycle
Using in situ hybridization we show that expression of the c‐ fos oncogene, a gene normally associated with osteosarcomas, is greatly elevated in osteoclasts of patients with Paget's disease. Immunohistochemical staining with c‐fos antibodies also shows increased protein in pagetic osteoclasts. In light of transgenic mouse experiments showing a key role for c‐fos in bone resorption, we propose that elevated c‐ fos gene expression in pagetic osteoclasts is an important component in producing the pagetic phenotype. Levels of c‐ fos gene and protein expression in pagetic osteoblasts are lower than those detected in osteoclasts but still higher than in nonpagetic osteoblasts. This may provide an explanation for the increased incidence of osteosarcomas in patients with Paget's disease because overexpression of c‐fos in osteoblasts of transgenic mice induces osteosarcoma formation.