Analysis of key cell‐cycle checkpoint proteins in colorectal tumours

McKay, Judith; Douglas, J.; Ross, Val G.; Curran, Stephanie; Loane, Joseph; Ahmed, Fareeda Y.; Cassidy, Jim; McLeod, Howard L.; Murray, Graeme I.

doi:10.1002/path.1053

Cited by 77 publications

(81 citation statements)

References 54 publications

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“…In this study, we have shown that low levels of cyclin D1 and p27 correlated to poor prognosis in conventional RCC using univariate analysis, and that p27 remained significantly associated to survival in the multivariate analyses. The association between low cyclin D1 and poor prognosis in the univariate analysis agrees with the data reported for breast cancer (Gillet et al, 1996;Nielsen et al, 1997;Hwang et al, 2002;McKay et al, 2002), although an association between high cyclin D1 and poor prognosis has been reported in many malignancies (Å kervall et al, 1997;Gansauge et al, 1997).…”

Section: Discussionsupporting

confidence: 86%

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

et al. 2003

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Aberrations in the G1/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of G1/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D1 and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of G1/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin D1 protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that G1/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes.

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Section: Discussionsupporting

confidence: 86%

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

et al. 2003

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“…PCNA is expressed in cycling cells and is used frequently to measure the proliferative activity of tissues (28). In addition, it is the most frequently observed protein among cell cycle -associated proteins (29). The PCNA promoter contains two CCAAT boxes at nucleotides À95 and À145 (30).…”

Section: Fig 2 Cytoplasmic Expression Of the Cyclin B2 Proteinmentioning

confidence: 99%

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Park¹,

Yu²,

Kim

et al. 2007

Clinical Cancer Research

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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)...

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“…Biotinylated goat anti-mouse secondary antibody, a complex of avidin with horseradish peroxidase (HRP) and diaminobenzidine (DAB) were used as the detection-staining system. The cellular localisation of L-FABP immunoreactivity was determined and scored for both intensity (negative, weak, moderate and strong) and proportion (0, 1 -5, 6 -25, 26 -50, 51 -75 and 76 -100%) of stained cells as previously described (Leeman et al, 2002;McKay et al, 2002). To allow comparison of L-FABP immunostaining with pathological stage and survival for each cancer integer values were assigned to the scores of intensity (0 -3) and proportion of tumour cells stained (0 -5).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Liver fatty acid binding protein expression in colorectal neoplasia

et al. 2004

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Liver fatty acid binding protein is a member of the fatty acid binding group of proteins that are involved in the intracellular transport of bioactive fatty acids and participate in intracellular signalling pathways, cell growth and differentiation. In this study we have used proteomics and immunohistochemistry to determine the changes in liver fatty acid binding protein in colorectal neoplasia. Comparative proteome analysis of paired samples colorectal cancer and normal colon identified consistent loss of liver fatty acid binding protein (L-FABP) in colorectal cancer compared with normal colon. To identify the changes in liver fatty acid binding protein expression during colorectal cancer development and progression the cell-specific expression of L-FABP was determined by immunohistochemistry in a series of colorectal cancers and colorectal adenomas. Decreased L-FABP immunoreactivity was significantly associated with poorly differentiated cancers (Po0.001). In colorectal adenomas there was a significant trend towards decreased staining of L-FABP in the larger adenomas (Po0.001). There was consistent L-FABP immunostaining of normal surface colonocytes. This study demonstrates that loss of L-FABP occurs at the adenoma stage of colorectal tumour development and also indicates that L-FABP is a marker of colorectal cancer differentiation.

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Analysis of key cell‐cycle checkpoint proteins in colorectal tumours

Cited by 77 publications

References 54 publications

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Liver fatty acid binding protein expression in colorectal neoplasia

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