Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: Is it a good predictor for tumor behavior?

Doğanay, Latife; Altaner, Semsi; Bilgi, Selcuk; Kaya, Esat; Ekuklu, Galip; Kutlu, Kemal

doi:10.1023/b:urol.0000020301.39181.03

Cited by 8 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CDKN3 is relative to hs_1‐tissue‐endocrine_and_cns, regulation of protein kinase activity, regulation of transferase activity, protein amino acid dephosphorylation, negative regulation of cell proliferation and regulation of cell proliferation (GenMAPP (http://www.genmapp.org/)). Studies into CDKN3 relationships in tumours has already been presented in a number of papers (1–13). However, distinct molecular networks and interpretation concerning CDKN3 in the cell cycle during non‐malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation have remained to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

et al. 2011

View full text Add to dashboard Cite

The relationship of cyclin-dependent kinase inhibitor 3 (CDKN3) with tumours has previously been presented in a number of publications. However, the molecular network and interpretation of CDKN3 through the cell cycle between non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) have remained to be elucidated. Here, we have constructed and analysed significant high expression gene CDKN3 activated and inhibited cell cycle networks from 25 HCC versus 25 non-malignancy associated hepatitis/cirrhosis patients (viral infection HCV or HBV) in GEO Dataset GSE10140-10141, by combination of a gene regulatory network inference method based on linear programming, and decomposition procedure using CapitalBio MAS 3.0 software, based on integration of public databases including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, and others. Comparing the same and differently activated and inhibited CDKN3 networks with GO analysis, between non-malignancy associated hepatitis/cirrhosis and HCC, our results suggest a CDKN3 cell cycle network (i) with stronger DNA replication and with weaker ubiquitin-dependent protein catabolism as common characteristics in both non-malignancy associated hepatitis/cirrhosis and HCC; (ii) with more cell division and weaker mitotic G2 checkpoint in non-malignancy associated hepatitis/cirrhosis; (iii) with stronger cell cycle and weaker cytokinesis, as a result forming multinucleate cells in HCC. Thus, it is useful to identify CDKN3 cell cycle networks for comprehension of molecular mechanism between non-malignancy associated hepatitis/cirrhosis and HCC transformation.

show abstract

Section: Introductionmentioning

confidence: 99%

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Doganay et al . reported high p27 kip1 immunoreactivity present in some highly aggressive bladder carcinomas 18 . High levels expression of p27 kip1 were also observed in a number of highly proliferative cancers of different organs 19–21 .…”

Section: Discussionmentioning

confidence: 93%

“…Doganay et al reported high p27 kip1 immunoreactivity present in some highly aggressive bladder carcinomas. 18 High levels expression of p27 kip1 were also observed in a number of highly proliferative cancers of different organs. [19][20][21] For example, Yatabe et al reported a higher level of p27 in small cell lung carcinomas that have a higher proliferative rate than nonsmall cell tumors.…”

Section: Discussionmentioning

confidence: 98%

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

Tseng

et al. 2007

Int J of Urology

View full text Add to dashboard Cite

Objectives: Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression and can be used as prognostic markers in various kinds of malignant tumors. This study investigated the expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27 kip1 , and cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low and high grade urothelial carcinoma, to see if their expression is associated with classification or grading of the urinary bladder urothelial carcinoma. Method: Nuclear expression of PCNA, p53, Rb, p27 kip1 , and cyclin D1 was determined immunohistochemically in a series of 89 urinary bladder tumor specimens, including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results of immunoreactivity were analyzed with respect to the associations with tumor grade. Results: Eighty-two percent (38/45) of the p27 kip1 positive tumors were urothelial carcinoma, and the percentage of the p27 kip1 positivity was higher with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of higher percentage of positive p53 immunoreactivity was noted in the urothelial carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and PCNA expression between benign, low malignant potential and urothelial carcinoma. Conclusion:We first noted an overexpression of p27 kip1 in urinary bladder urothelial carcinoma. The result indicates that some urothelial carcinomas may tolerate this inhibitor of cell cycle progression.

show abstract

“…On the other hand, Doganay et al, provided evidence that expression of p27 is generally low in urinary bladder carcinoma but is not related to tumor grade, stage, PCNA index, recurrence rate and prognosis. They concluded that p27 expression may not be an independent predictor of outcome with transitional cell carcinoma of the urinary bladder 31…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of p27^kip1 knockout mice to urinary bladder carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine may not simply be due to enhanced proliferation

Hikosaka

Ogawa

Sugiura

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Deregulated proliferation is one of the fundamental characteristics of carcinogenesis. p27 is one of the most well characterized negative cell cycle regulator. In our previous study, expression of p27 protein was found to be dramatically suppressed on stimulation of cell proliferation by calculi in the rodent urinary bladder, withdrawal of the insult resulting in re-expression of p27 and regression of urothelial hyperplastic lesions. In the present study, to evaluate how loss of function impacts on urinary bladder carcinogenesis, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a bladder carcinogen was given to p27 knockout mice. Males and females with either null, hetero or wild-type p27 alleles were divided into 2 groups, one given drinking water containing 0.05% BBN for 10 weeks and the other receiving distilled water, then, killed at week 20. The experiment was repeated for confirmation of the outcome. In the second experiment, performed with a larger number of animals, the incidence of urinary bladder carcinomas was significantly higher in female p27-null mice than in their wildtype counterparts. p27 deficiency also resulted in their increase of relative weights of urinary bladders and section areas of carcinomas in BBN-treated mice. Interestingly, while BrdU labeling indices generally increased with progression of mucosal proliferative lesions, from normal epithelium, through hyperplasia to carcinoma, there was no significant variation with the p27 genotype, in tumors as well as normal urothelium. These findings suggest that p27 deficient mice have elevated susceptibility to BBN-induction of urinary bladder carcinogenesis through a mechanism which might be independent of acceleration of cell cycling. ' 2007 Wiley-Liss, Inc.

show abstract

Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: Is it a good predictor for tumor behavior?

Abstract: The results indicate that p27 is not a good predictor for outcome of transitional cell carcinoma of the bladder.

Cited by 8 publications

References 27 publications

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

Susceptibility of p27^kip1 knockout mice to urinary bladder carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine may not simply be due to enhanced proliferation

Contact Info

Product

Resources

About

Expression of the cyclin-dependent kinase inhibitor p27 in transitional cell bladder cancers: Is it a good predictor for tumor behavior?

Abstract: The results indicate that p27 is not a good predictor for outcome of transitional cell carcinoma of the bladder.

Cited by 8 publications

References 27 publications

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

Susceptibility of p27kip1 knockout mice to urinary bladder carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine may not simply be due to enhanced proliferation

Contact Info

Product

Resources

About

Susceptibility of p27^kip1 knockout mice to urinary bladder carcinogenesis induced by N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine may not simply be due to enhanced proliferation