Kawaguchi Ken-Ichi, Oda Yoshinao, Saito Tsuyoshi, Yamamoto Hidetaka, Takahira Tomonari, Tamiya Sadafumi, Iwamoto Yukihide, Tsuneyoshi Masazumi
Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Hum Pathol. 2004 Jan;35(1):61-8. doi: 10.1016/j.humpath.2003.07.004.
Transforming growth factor (TGF)-beta 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-beta1, TGF-beta-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-beta1, TGF-beta-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-beta-IR and -IIR showed a tendency to be greater in MGCs than in MSCs; however, no differences were observed in TGF-beta1. 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-beta-IIR and p27 was concordantly decreased in both MGSs and MSCs (P = 0.0014 and 0.0317, respectively). The expression for TGF-beta-IIR and p27 in Western blot analysis was related to the results from immunohistochemical analysis, and the expression of TGF-beta-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-beta-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.
转化生长因子（TGF）-β是一种潜在的细胞生长调节因子，它通过由I型和II型受体（IR和IIR）组成的异源复合物传递信号。本研究采用免疫组织化学和蛋白质印迹分析，检测了骨巨细胞瘤（GCT）中TGF-β1、TGF-β-IR和-IIR与细胞周期相关蛋白之间的相关性。首先，对92例骨巨细胞瘤进行了TGF-β1、TGF-β-IR和-IIR、p27KIP1（p27）、p21WAF1（p21）、细胞周期蛋白D1和细胞周期蛋白E的免疫组织化学研究；分别评估这些蛋白在多核巨细胞（MGCs）和单核基质细胞（MSCs）中的表达；并使用MIB-１评估增殖活性。接下来，为了证实我们的免疫组织化学结果，对19例有冷冻样本的病例进行了蛋白质印迹分析。TGF-β-IR和-IIR的免疫反应性在MGCs中显示出比MSCs中更强的趋势；然而，TGF-β1未观察到差异。细胞周期蛋白D1的表达与MGCs和MSCs中血管侵犯的发生相关（分别为P = 0.0255和0.0183）。TGF-β-IIR和p27在MGSs和MSCs中的表达均一致降低（分别为P = 0.0014和0.0317）。蛋白质印迹分析中TGF-β-IIR和p27的表达与免疫组织化学分析结果相关，并且在几乎所有骨巨细胞瘤病例中TGF-β-IIR和p27的表达都是一致的。此外，在MSCs中p27表达与MIB-1标记指数之间存在统计学上显著的负相关（P = 0.0397）。在骨巨细胞瘤中，TGF-β-IIR和p27表达一致降低；这一结果支持了这两个因子可能在该肿瘤细胞增殖中起重要作用的可能性。此外，我们的结果提供了细胞外生长因子的作用与细胞周期控制之间的可能联系。此外，p27表达可能是该肿瘤MSCs中细胞增殖的一个有用指标。
