NF-Y-dependent cyclin B2 expression in colorectal adenocarcinoma

被引:50
作者
Park, Seon-Hwa
Yu, Gyung-Ran
Kim, Woo-Ho
Moon, Woo-Sung
Kim, Jong-Hun
Kim, Dae-Ghon
机构
[1] Chonbuk Natl Univ, Sch Med & Hosp, Res Inst Clin Med,Brain Korea Program Med Sci 21, Dept Internal Med,Div Gastroenterol & Hepatol, Jeonju 561172, Jeonbuk, South Korea
[2] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South Korea
[3] Chonbuk Natl Univ, Sch Med & Hosp, Res Inst Clin Med,Brain Korea Program Med Sci 21, Dept Pathol,Div Gastroenterol & Hepatol, Jeonju 561172, Jeonbuk, South Korea
[4] Chonbuk Natl Univ, Sch Med & Hosp, Res Inst Clin Med,Brain Korea Program Med Sci 21, Dept Surg,Div Gastroenterol & Hepatol, Jeonju 561172, Jeonbuk, South Korea
关键词
D O I
10.1158/1078-0432.CCR-06-1461
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Cyclin B2, a G(2)-M cyclin, is overexpressed in colorectal adenocarcinomas compared with the normal mucosa. This study examined the level of cyclin B2 overexpression according to the histologic findings and investigated the mechanism(s) and clinical implications of cyclin 62 overexpression in colorectal adenocarcinomas. Experimental Design: The immunoreactivity of the polyclonal antibodies to cyclin B2 was determined in colorectal cancer cells. The transcriptional regulation of cyclin B2 by NF-Y was analyzed using an in vitro transfection assay and an in vivo chromatin immunoprecipitation assay. The proliferative activity of the colorectal cancer cells in relation to cyclin B2 overexpression was further examined. Results: The cytoplasmic distribution of cyclin B2 immunoreactivity was positive in 42 of 65 (64.6%) cases of colorectal adenocarcinoma, and the level was similar regardless of the histologic type. A dominant-negative form of NF-YA effectively inhibited the cyclin B2 promoter activity, and NF-Y was found to bind three conserved CCAAT boxes in the cyclin B2 promoter in colorectal adenocarcinoma cells. Tumor cells with a higher functional cyclin B2 activity grew faster than those with a lower activity. Furthermore, there was a correlation between the cells showing immunoreactivity to cyclin 132 and those containing the proliferating cell nuclear antigen, a G(1)-S cyclin, which is also downstream of NF-Y in colorectal adenocarcinoma cells. Conclusions: Cyclin 132 seems to be a molecular marker of a colorectal adenocarcinoma and that its up-regulation and coordinate expression of the other cell cycle - related genes by NF-Y might contribute to tumor cell proliferation by accelerating cell cycle progression.
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收藏
页码:858 / 867
页数:10
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