title: Decreased expression of transforming growth factor-beta II receptor is associated with that of p27KIP1 in giant cell tumor of bone: a possible link between transforming growth factor-beta and cell cycle-related protein.
abstract: 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.
authors.affiliation: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tomonari
authors.initials: T
authors.lastname: Takahira
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Tamiya
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002648:Child; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27