Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma
Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma
复制标题
DOI：
10.1111/j.1349-7006.2011.02046.x
复制
发表时间：
2011-11-01
期刊：
影响因子：
5.7
通讯作者：
Yoshino, Tadashi
中科院分区：
文献类型：
--
作者：
Igawa, Takuro;Sato, Yasuharu;Yoshino, Tadashi
D细胞周期蛋白是参与某些淋巴瘤发病的重要细胞周期调节蛋白。细胞周期蛋白D1过表达是套细胞淋巴瘤的标志，而细胞周期蛋白D2和D3并未显示与任何特定亚型淋巴瘤密切相关。在本研究中，我们发现cyclin D2在所有慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）病例的增殖中心（PC）特异性过表达（19/19）。为了研究这种过表达的分子机制，我们用免疫组织化学方法检测了核因子(NF)- κ B、p15、p16、p18和p27在6例PC患者中的表达。5例出现NF-kappa B表达上调，已知NF-kappa B通过结合CCND2启动子区直接诱导细胞周期蛋白D2。6例PC均显示p27表达下调。相比之下，p15表达上调在6个PC中检测到5个。这一差异表明，未知的细胞周期调节机制也涉及NF-kappa B相关通路，因为NF-kappa B不仅直接上调周期蛋白D2，还通过c-Myc间接上调，而c-Myc被认为下调了p27和p15。总之，细胞周期蛋白D2在CLL/SLL的PC中过度表达，这种过度表达部分是由于nf - κ b相关通路的上调。（癌症科学2011；102:2103-2107）
The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-kappa B, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-kappa B expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-kappa B-related pathways are also involved, because NF-kappa B upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-kappa B-related pathways. (Cancer Sci 2011; 102: 2103-2107)