NF-Y-dependent cyclin B2 expression in colorectal adenocarcinoma.
OBJECTIVE
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 B2 overexpression in colorectal adenocarcinomas.


METHODS
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 B2 and those containing the proliferating cell nuclear antigen, a G1-S cyclin, which is also downstream of NF-Y in colorectal adenocarcinoma cells.


CONCLUSIONS
Cyclin B2 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.
Park
Seon-Hwa
SH
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Research Institute of Clinical Medicine, Brain Korea 21 Program for Medical Science, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
Yu
Gyung-Ran
GR
Kim
Woo-Ho
WH
Moon
Woo-Sung
WS
Kim
Jong-Hun
JH
Kim
Dae-Ghon
DG
D000328:Adult; D000368:Aged; D023081:CCAAT-Binding Factor / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019926:Cyclin B / Q000096:biosynthesis*; D056765:Cyclin B2; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution; D014158:Transcription, Genetic
D023081:CCAAT-Binding Factor; C503758:CCNB2 protein, human; D019926:Cyclin B; D056765:Cyclin B2