Ohshima K, Haraoka S, Fujiki T, Yoshioka S, Suzumiya J, Kanda M, Kikuchi M
Department of Pathology, School of Medicine, Fukuoka University, Nanakuma, Japan.
Pathol Int. 1999 Jun;49(6):506-12. doi: 10.1046/j.1440-1827.1999.00898.x.
p21 Is involved in the control of the mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases. The cyclins are dependent on the phases of the cell cycle, and divided into two classes: mitotic cyclins (A, B1, B2) and G1 cyclins (C, D1, D2, D3, E). The product of the p21 gene is a potent downstream effector of the p53 tumor-suppressor gene function. The Hodgkin and Reed- Sternberg (H & RS) cells in Hodgkin's disease are reported to frequently express p53, p21, and nuclear proliferative activity (Ki-67). To clarify the relationship of p21, p53 and cyclins, we performed the immunohistochemistry of p53, p21, Ki-67, cyclin D1, cyclin E, cyclin A and cyclin B1, using 11 cases with Hodgkin's disease. In addition, we performed p53 gene sequencing of exon 5-8, and in situ hybridization of Epstein-Barr virus (EBV) EBER-1 region, whose products have reported to induce the expression of cyclin D. In this study, in all cases, Ki-67 was expressed in almost all H & RS cells, and p53 and p21 were expressed in H & RS cells. No p53 gene mutations were detected in any case, and p53 protein overexpression did not correlate with p53 gene mutations. The number of p21-positive H & RS cells was significantly related with that of the p53-positive cells. The cyclins E, A, B1 and D1 were also expressed in H & RS cells. Unexpectedly, the expression of the cyclins was not suppressed by p21 and p53 expression. In addition, the existence of EBV was not related to the expression of cyclins. It is considered that H & RS cells are, indeed, in cell cycle and commonly express the cell cyclins, and that the cell cycle of H & RS cells may not be specifically fixed in the G1, S, G2 or M phases.
p21 通过结合并抑制细胞周期蛋白依赖性激酶参与哺乳动物细胞周期的调控。细胞周期蛋白依赖于细胞周期的阶段，分为两类：有丝分裂细胞周期蛋白（A、B1、B2）和G1 期细胞周期蛋白（C、D1、D2、D3、E）。p21 基因的产物是 p53 肿瘤抑制基因功能的有力下游效应物。据报道，霍奇金病中的霍奇金和里德 - 斯腾伯格（H & RS）细胞经常表达 p53、p21 和核增殖活性（Ki-67）。为了阐明 p21、p53 与细胞周期蛋白之间的关系，我们对 11 例霍奇金病患者进行了 p53、p21、Ki-67、细胞周期蛋白 D1、细胞周期蛋白 E、细胞周期蛋白 A 和细胞周期蛋白 B1 的免疫组织化学检测。此外，我们对第 5 - 8 外显子进行了 p53 基因测序，并对 Epstein-Barr 病毒（EBV）EBER-1 区域进行了原位杂交，其产物据报道可诱导细胞周期蛋白 D 的表达。在本研究中，所有病例中，几乎所有 H & RS 细胞均表达 Ki-67，且 H & RS 细胞中表达 p53 和 p21。任何病例均未检测到 p53 基因突变，p53 蛋白过表达与 p53 基因突变无关。p21 阳性的 H & RS 细胞数量与 p53 阳性细胞数量显著相关。细胞周期蛋白 E、A、B1 和 D1 在 H & RS 细胞中也有表达。出乎意料的是，细胞周期蛋白的表达并未受到 p21 和 p53 表达的抑制。此外，EBV 的存在与细胞周期蛋白的表达无关。据认为，H & RS 细胞确实处于细胞周期中，通常表达细胞周期蛋白，并且 H & RS 细胞的细胞周期可能不会特异性地固定在 G1、S、G2 或 M 期。
