Suzuki R, Kuroda H, Komatsu H, Hosokawa Y, Kagami Y, Ogura M, Nakamura S, Kodera Y, Morishima Y, Ueda R, Seto M
Laboratory of Chemotherapy, Aichi Cancer Center, Nagoya, Japan.
Leukemia. 1999 Sep;13(9):1335-42. doi: 10.1038/sj.leu.2401485.
Three D-type cyclins, cyclin D1, D2 and D3, belong to the G1 cyclin, which regulates the G1/S transition of the cell cycle, and feature highly homologous amino acid sequences. The cyclin D1 gene was found to be transcriptionally activated in B-lymphoid malignancies with t(11;14), but available information is limited regarding expression of cyclin D2 and D3 in hematopoietic malignancies. We examined the expressions of three D-type cyclins to investigate how these homologous genes are differentially used. Northern blot hybridization with densitometric analyses was performed to examine 64 cell lines and 159 patients with various hematopoietic malignancies. Among lymphoid malignancies, cyclin D1 overexpression was exclusively detected in B cell malignancies accompanied by a genetic event consisting of 11q13 chromosomal translocation, consisting of 13 of 19 (68%) patients with mantle cell lymphoma, two of 11 (18%) with B-chronic lymphocytic leukemia, and one of six (17%) with multiple myeloma. The cyclin D2 expression was significantly higher in T cell malignancies than in B cell malignancies (P = 0.003 for cell lines and P < 0.0001 for patient samples, respectively). In the T cell malignancies, cyclin D2 overexpression was predominantly recognized in those with mature phenotype. Furthermore, cyclin D2 expression was upregulated by phytohemagglutinin (PHA) stimulation of normal T-lymphocytes, suggesting that this simply represents the proliferation status of mature T cells. Although cyclin D3 was ubiquitously expressed, its expression was reduced in lymphoid malignancies with cyclin D1 or D2 overexpression. In myeloid leukemias, although three D-type type cyclins were differentially expressed, no preference for particular D-type cyclins was found. This selective usage of D-type cyclins in lymphoid malignancies suggests an existence of a regulatory mechanism among three D-type cyclins.
三种D型细胞周期蛋白，即细胞周期蛋白D1、D2和D3，属于G1期细胞周期蛋白，可调节细胞周期的G1/S转换，其氨基酸序列具有高度同源性。细胞周期蛋白D1基因在伴有t(11;14)的B淋巴细胞恶性肿瘤中被发现转录激活，但关于细胞周期蛋白D2和D3在造血系统恶性肿瘤中的表达，现有信息有限。我们检测了三种D型细胞周期蛋白的表达，以研究这些同源基因是如何被差异利用的。采用Northern印迹杂交及光密度分析，对64株细胞系和159例不同造血系统恶性肿瘤患者进行检测。在淋巴系统恶性肿瘤中，细胞周期蛋白D1过表达仅在伴有11q13染色体易位这一基因事件的B细胞恶性肿瘤中检测到，其中19例套细胞淋巴瘤患者中有13例(68%)、11例B慢性淋巴细胞白血病患者中有2例(18%)、6例多发性骨髓瘤患者中有1例(17%)。细胞周期蛋白D2在T细胞恶性肿瘤中的表达显著高于B细胞恶性肿瘤(细胞系中P = 0.003，患者样本中P < 0.0001)。在T细胞恶性肿瘤中，细胞周期蛋白D2过表达主要见于具有成熟表型的肿瘤。此外，植物血凝素(PHA)刺激正常T淋巴细胞可上调细胞周期蛋白D2的表达，提示这仅仅代表成熟T细胞的增殖状态。虽然细胞周期蛋白D3普遍表达，但其在细胞周期蛋白D1或D2过表达的淋巴系统恶性肿瘤中表达降低。在髓系白血病中，虽然三种D型细胞周期蛋白表达存在差异，但未发现对特定D型细胞周期蛋白有偏好。D型细胞周期蛋白在淋巴系统恶性肿瘤中的这种选择性利用提示三种D型细胞周期蛋白之间存在调控机制。
