Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors

Alterations of cell cycle regulatory proteins, especially those that regulate G1 to S transition, have been implicated in the pathogenesis of a wide variety of human tumors. In previous studies we showed that that there is overexpression of cyclin D1 protein predominately in the giant cell component of giant cell tumors of bone. The purpose of this study was to investigate the mechanisms that may be responsible for cyclin D1 accumulation in giant cell tumors. Giant cell tumors have high levels of cyclin D1 mRNA and the giant cell-enriched population of these tumors have significantly more mRNA and protein expression of cyclin D1 than the mononuclear cell population. The giant cells also expressed higher levels of p21 protein and more p21 bound to cyclin D1 than the mononuclear cells. It is possible that p21 may be contributing to the cyclin D1 accumulation that occurs in the giant cells and perhaps even giant cell formation in these tumors. Additional studies are required to confirm the role of p21 in the pathogenesis of these tumors. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.