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 B2 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 B2 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 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.Mitosis is induced by the activation of the M-phasepromoting factor, which is a protein kinase whose principal subunits are p34 cdc2 and cyclin B. Cyclin B is a regulatory subunit that varies in abundance throughout the cell cycle (1). The metaphase to anaphase transition marks the end of mitosis and is induced by the degradation of cyclin B, which in turn leads to the inactivation of M-phase -promoting factor. As the cell cycle progresses, cyclin B begins to accumulate when the cell enters the interphase, which is followed by the reactivation of M-phase -promoting factor and another round of mitosis. Therefore, the B-type cyclins are the primary mitotic cyclins, although several yeast B-type cyclins have been reported to function earlier in the cell cycle, particularly in the S phase (2, 3). There are two mammalian B-type cyclins, cyclins B1 and B2, which differ in their NH 2 termini but have 57% similarity (4 -6). Cyclins B1 and B2 are coexpressed in most dividing cells and, in association with cdc2, play a role in entering the G 2 -M phase, although their subcellular localization differs (7). Cyclin B1 is primarily cytoplasmic but constantly shuttles between the nucleus and the cytoplasm during the interphase. At the end of the prophase, cyclin B1 rapidly translocates to the nucleus (8, 9)...

The aim of this study was to identify molecular markers associated with oncogenic differentiation in hepatocellular carcinoma (HCC). Using an unsupervised clustering method with a cDNA microarray, HCC (T) gene expression profiles and corresponding non-tumor tissues (NT) from 40 patients were analyzed. Of total 217 genes, 72 were expressed preferentially in HCC tissues. Among 186 differentially regulated genes, there were molecular chaperone and tumor suppressor gene clusters in the Edmondson grades I and II (GI/II) subclass compared with the liver cirrhosis (LC) subclass. The Edmondson grades III and IV (GIII/IV) subclass with a poor survival (P = 0.0133) contained 122 differentially regulated genes with a cluster containing various metastasis-and invasion-related genes compared with the GI/II subclass. Immunohistochemical analysis revealed that ANXA2, one of the 72 genes preferentially expressed in HCC, was over-expressed in the sinusoidal endothelium and in malignant hepatocytes in HCC. The genes identified in the HCC subclasses will be useful molecular markers for the genesis and progression of HCC. In addition, ANXA2 might be a novel marker for tumor angiogenesis in HCC.