MIB-1 (KI-67) Proliferation Index and Cyclin-Dependent Kinase Inhibitor p27Kip1 Protein Expression in Nephroblastoma

CONTEXT AND OBJECTIVE: Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors. DESIGN AND SETTING: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. METHODS: 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. RESULTS: The frequencies of the heterozygote (Ser/Arg) and polymorphic homozygote (Arg/Arg) genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T) and 0.6% (T/T). These frequencies were not statistically different (P > 0.05) from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site). Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively). CONCLUSION: No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.

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Effects of cyclin-dependent kinase inhibitor Purvalanol B application on protein expression and developmental progression in intra-erythrocytic Plasmodium falciparum parasites

Malaria Journal ◽

10.1186/s12936-015-0655-x ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Kristen M Bullard ◽

Carolyn Broccardo ◽

Susan M Keenan

Keyword(s):

Plasmodium Falciparum ◽

Protein Expression ◽

Kinase Inhibitor ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor ◽

Developmental Progression

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Knockout of the caspase 8‐associated protein 2 gene improves recombinant protein expression in HEK293 cells through up‐regulation of the cyclin‐dependent kinase inhibitor 2A gene

Biotechnology and Bioengineering ◽

10.1002/bit.27561 ◽

2020 ◽

Vol 118 (1) ◽

pp. 186-198

Author(s):

Laura Abaandou ◽

Ashish K. Sharma ◽

Joseph Shiloach

Keyword(s):

Recombinant Protein ◽

Protein Expression ◽

Kinase Inhibitor ◽

Recombinant Protein Expression ◽

Hek293 Cells ◽

Caspase 8 ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor

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Application of Proteomics in the Search for Novel Proteins Associated with the Anti-cancer Effect of the Synthetic Cyclin-dependent Kinases Inhibitor, Bohemine

Technology in Cancer Research & Treatment ◽

10.1177/153303460200100405 ◽

2002 ◽

Vol 1 (4) ◽

pp. 247-256 ◽

Cited By ~ 6

Author(s):

Hana Kovarova ◽

Petr Halada ◽

Petr Man ◽

Petr Dzubak ◽

Marian Hajduch

Keyword(s):

Mass Spectrometry ◽

Cell Cycle ◽

Protein Expression ◽

Cell Line ◽

Metabolic Pathways ◽

Kinase Inhibitor ◽

A549 Cells ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor ◽

Anti Cancer

The purpose of this study was to use the proteomics approach, which is based on high resolution two-dimensional electrophoresis coupled with multivariate correspondence analysis and mass spectrometry, to classify objectively the biochemical basis of the anti-cancer activity of the synthetic cyclin-dependent kinase inhibitor, bohemine (BOH). The changes in the cell cycle and corresponding protein composition of the A549 human lung adenocarcinoma cell line after treatment with BOH were evaluated and proteins differentially expressed in the BOH treated A549 cells, compared to the untreated A549 counterparts, were selected. Thirteen of these candidate proteins associated with the drug effects in vitro were identified by mass spectrometry. Many of these proteins fall into one of three functional categories: i) metabolic pathways (glycolysis, nucleic acid synthesis and NADPH production), ii) stress response and protein folding, and iii) cytoskeleton and exocytosis. Changes in protein expression patterns corresponded to a higher resistance of A549 lung carcinoma cells to BOH when compared to the CEM leukaemia cell line. These protein changes reflect a fine balance of the resistant versus the susceptible phenotype in response to the drug. Since BOH is a selective cyclin-dependent kinase inhibitor, changes in the protein expression pattern can be more generally associated with cell cycle regulation as evidenced by inhibition of cell cycling in A549 cells. Our conclusions further underline the importance of cell cycle control in both the cellular signalling and metabolic pathways.

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Reduced Expression of Cyclin-dependent Kinase Inhibitor p27Kip1 in Feline Lymphoma

Veterinary Pathology ◽

10.1354/vp.38-6-698 ◽

2001 ◽

Vol 38 (6) ◽

pp. 698-702 ◽

Cited By ~ 6

Author(s):

B. Madewell ◽

S. Griffey ◽

J. Walls ◽

R. Gandour-Edwards

Keyword(s):

Cell Cycle ◽

Marginal Zone ◽

Kinase Inhibitor ◽

Lymphoid Hyperplasia ◽

Lymphoid Tissues ◽

Cyclin Dependent Kinase ◽

Mantle Zone ◽

Ki 67 ◽

Cyclin Dependent Kinase Inhibitor ◽

Reactive Lymphocytes

Expression of p27Kip1 was identified in feline lymphoid tissues by immunohistochemistry. In normal lymphoid tissues, p27Kip1 was detected as a distinct nuclear stain in lymphocytes of the follicular mantle zone and interfollicular small lymphocytes, whereas activated lymphoblasts in the germinal center were negative. Lymphoid hyperplasia was similarly immunolabeled but with an expanded mantle zone and marginal zone of p27Kip1-reactive lymphocytes. Both T- and B-cell lymphomas lacked p27Kip1 immunolabel and were determined to be proliferative based on immunohistochemical detection of the Ki-67 antigen. Scattered p27Kip1- immunolabeled lymphocytes were detected throughout the lamina propria of most specimens characterized as lymphoplasmacytic enteritis. The results of this study suggest that the antiproliferative effect of the cell cycle regulator p27Kip1 is abrogated in feline lymphoma, presumably allowing cells to bypass the G1-S checkpoint of the cell cycle.

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Inhibition of F-Box Protein p45SKP2 Expression and Stabilization of Cyclin-Dependent Kinase Inhibitor p27KIP1 in Vitamin D Analog-Treated Cancer Cells

Endocrinology ◽

10.1210/en.2002-0026 ◽

2003 ◽

Vol 144 (3) ◽

pp. 749-753 ◽

Cited By ~ 40

Author(s):

Roberto Lin ◽

Tian Tian Wang ◽

Wilson H. Miller ◽

John H. White

Keyword(s):

Head And Neck ◽

Cancer Cells ◽

Gene Transcription ◽

Kinase Inhibitor ◽

Cyclin Dependent Kinase ◽

P27kip1 Protein ◽

Protein Levels ◽

Cyclin Dependent Kinase Inhibitor ◽

Squamous Carcinoma Cells ◽

F Box Protein

Treatment of cancer cells with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or its analogs induces growth arrest and expression of the cyclin-dependent kinase inhibitor p27KIP1. Although 1,25(OH)2D3 transiently enhances p27kip1 gene transcription in some cells, its effects on p27KIP1 protein levels are generally more gradual and sustained. This suggests that 1,25(OH)2D3 treatment may be stabilizing p27KIP1 protein, which is sensitive to modification by the SCFSKP2 protein ubiquitin ligase and proteosomal degradation. Here, we show that treatment of AT-84 head and neck squamous carcinoma cells with the 1,25(OH)2D3 analog EB1089 increases p27KIP1 protein levels without significantly affecting expression of its mRNA. EB1089 treatment repressed expression of mRNAs encoding the F-box protein p45SKP2, a marker of poor head and neck cancer prognosis, and the cyclin kinase subunit CKS1, which is essential for targeting p45SKP2 to p27KIP1. This coincided with a reduction of total p45SKP2 protein, and p45SKP2 associated with p27KIP1. Consistent with these findings, turnover of p27KIP1 protein was strongly inhibited in the presence of EB1089. A similar reduction in p45SKP2 expression and stabilization of p27KIP1 protein was observed in 1,25(OH)2D3-sensitive UF-1 promyelocytic leukemia cells, which also respond by transiently increasing p27kip1 gene transcription. Our results reveal that 1,25(OH)2D3 analogs increase levels of p27KIP1 in different cell types by inhibiting expression of SCFSKP2 subunits and reducing turnover of p27KIP1 protein.

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