Transforming growth factor (TGF)-β is a potential regulator of cell growth that sends its signals through a heteromeric complex composed of type I and II receptors (IR and IIR). This study examined a correlation between TGF-β1, TGF-β-IR and -IIR, and cell cycle-related proteins in giant cell tumor (GCT) of bone, using immunohistochemical and Western blot analysis. First, an immunohistochemical study for TGF-β1, TGF-β-IR and -IIR, p27KIP1 (p27), p21WAF1 (p21), cyclin D1, and cyclin E was carried out on 92 cases of GCT of bone; the expression of these proteins was evaluated in multinucleated giant cells (MGCs) and mononucleated stromal cells (MSCs) separately; and proliferative activity was assessed using MIB-1. Next, to confirm our immunohistochemical results, Western blot analysis was performed in 19 cases for which frozen samples were available. Immunoreactivity for TGF-β-IR and -IIR showed a tendency to be greater in MGCs than in MSCs; however, no differences were observed in TGF-β1. Cyclin D1 expression was correlated with the occurrence of vascular invasion in both MGCs and MSCs (P = 0.0255 and 0.0183, respectively). The expression of TGF-β-IIR and p27 was concordantly decreased in both MGSs and MSCs (P = 0.0014 and 0.0317, respectively). The expression for TGF-β-IIR and p27 in Western blot analysis was related to the results from immunohistochemical analysis, and the expression of TGF-β-IIR and p27 was concordant in almost all GCT cases. Furthermore, there was a statistically significant inverse relationship between p27 expression and MIB-1 labeling index in MSCs (P = 0.0397). In GCT of bone, TGF-β-IIR and p27 expression were concordantly decreased; this result supports the possibility that these 2 factors may play an important role in cell proliferation of this tumor. Furthermore, our results provide a possible link between the effects of extracellular growth factors and cell cycle control. In addition, p27 expression may be a useful indicator of cell proliferation in MSCs of this tumor.
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine