RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53

Aberrant activation of cell cycle molecules has been postulated to play a role in apoptosis (“catastrophic cell cycle”). Here we show that in noncycling developing thymocytes, the cyclin- dependent kinase Cdk2 is activated in response to all specific and nonspecific apoptotic stimuli tested, including peptide-specific thymocyte apoptosis. Cdk2 was found to function upstream of the tumor suppressor p53, transactivation of the death promoter Bax, alterations of mitochondrial permeability, Bcl-2, caspase activation, and caspase-dependent proteolytic cleavage of the retinoblastoma protein. Inhibition of Cdk2 completely protected thymocytes from apoptosis, mitochondrial changes, and caspase activation. These data provide the first evidence that Cdk2 activity is crucial for the induction of thymocyte apoptosis.

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The tumor suppressor p53 connects ribosome biogenesis to cell cycle control: a double-edged sword

Oncotarget ◽

10.18632/oncotarget.107 ◽

2010 ◽

Vol 1 (1) ◽

pp. 43-47 ◽

Cited By ~ 16

Author(s):

Michael Hölzel ◽

Kaspar Burger ◽

Bastian Mühl ◽

Mathias Orban ◽

Markus Kellner ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Ribosome Biogenesis ◽

Cell Cycle Control ◽

Tumor Suppressor P53

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Analysis of microRNA regulating cell cycle-related tumor suppressor genes in endometrial cancer patients

Human Cell ◽

10.1007/s13577-020-00451-6 ◽

2020 ◽

Author(s):

Łukasz Witek ◽

Tomasz Janikowski ◽

Iwona Gabriel ◽

Piotr Bodzek ◽

Anita Olejek

Keyword(s):

Cell Cycle ◽

Endometrial Cancer ◽

Tumor Suppressor ◽

Cancer Progression ◽

Tumor Suppressor Genes ◽

Target Genes ◽

Endometrial Adenocarcinoma ◽

Developed Countries ◽

Differentially Expressed ◽

Suppressor Genes

Abstract Endometrial cancer remains the most common malignancy of the female genital system in developed countries. Tumor suppressor genes are responsible for controlling the cells fate in the cell cycle and preventing cancerogenesis. Gene expression affects cancer progression and is modulated by microRNAs defined as both tumor suppressors and oncogenes. These molecules indirectly regulate multiple processes like cell proliferation, differentiation and apoptosis. The aim of this study was to analyze miRNAs expression that can regulate the activity of tumor suppressor genes related to the cell cycle in patients with endometrioid endometrial cancer. The study group consisted of 12 samples that met the inclusion criteria from a total of 48 obtained. The 12 samples were used to analyze microRNA expression. Complementary miRNAs were identified using TargetScan Database and statistical analysis. MicroRNAs were determined for the tumor suppressor genes: CYR61, WT1, TSPYL5, HNRNPA0, BCL2L1 and BAK1. All the miRNAs were complementary to the described target genes based on TargetScan Database. There were five miRNAs differentially expressed that can regulate tumor suppressor genes related to the cell cycle. The distinguished miRNAs: mir-340-3p, mir-1236-5p, mir-874-3p, mir-873-5p.2 and mir-548-5p were differentially expressed in endometrial cancer in comparison to the control. Among the distinguished miRNAs, the most promising is mir-874-3p, which may have an important role in endometrial adenocarcinoma proliferation.

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Tumor-suppressor p53 is expressed in proliferating and newly formed neurons of the embryonic and postnatal rat brain: Comparison with expression of the cell cycle regulators p21Waf1/Cip1, p27Kip1, p57Kip2, p16Ink4a, cyclin G1, and the proto-oncogene bax

The Journal of Comparative Neurology ◽

10.1002/(sici)1096-9861(19980727)397:2<181::aid-cne3>3.0.co;2-x ◽

1998 ◽

Vol 397 (2) ◽

pp. 181-198 ◽

Cited By ~ 81

Author(s):

Menno Van Lookeren Campagne ◽

Ramanjit Gill

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Rat Brain ◽

Cell Cycle Regulators ◽

Tumor Suppressor P53 ◽

Cyclin G1

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The prolyl cis/trans isomerase cyclophilin 18 interacts with the tumor suppressor p53 and modifies its functions in cell cycle regulation and apoptosis

Oncogene ◽

10.1038/onc.2009.248 ◽

2009 ◽

Vol 28 (44) ◽

pp. 3915-3925 ◽

Cited By ~ 18

Author(s):

N Baum ◽

C Schiene-Fischer ◽

M Frost ◽

M Schumann ◽

K Sabapathy ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Cell Cycle Regulation ◽

Tumor Suppressor P53 ◽

Cycle Regulation

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P53 AND CYCLIN B1 MEDIATE APOPTOTIC EFFECTS OF APIGENIN AND RUTIN IN ER+-BREAST CANCER MCF-7 CELLS

Jurnal Teknologi ◽

10.11113/jt.v80.10704 ◽

2017 ◽

Vol 80 (1) ◽

Cited By ~ 4

Author(s):

Narimah Abdul Hamid Hasani ◽

Indah Mohd Amin ◽

Roziana Kamaludin ◽

Nik Mohd Mazuan Nik Mohd Rosdyd ◽

Mohammad Johari Ibahim ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Suppressor ◽

Estrogen Receptor Alpha ◽

Annexin V ◽

Cyclin B1 ◽

Tumor Suppressor P53 ◽

Proliferative Effect ◽

Tamoxifen Efficacy ◽

Mcf 7

Tamoxifen is an effective treatment for estrogen receptor alpha positive (ERa+)-breast cancer, however patients who received the treatment for five years have greater mortality risk compared to those who did not receive tamoxifen. Furthermore, patients treated with tamoxifen developed resistance to the drug which mediated through p53 and PTEN. Therefore, the study is undertaken to determine the potential adjuvant properties of flavonoids, apigenin and rutin to promote the anticancer activity induced by tamoxifen using ERa+-breast cancer MCF-7 cell lines. MCF-7 and non-transformed breast MCF-10A cells were treated separately with apigenin, rutin, tamoxifen or the combination of each flavonoids with tamoxifen. Anti-proliferative activity and respective IC50 concentrations were determined using MTT assay. The respective IC50 concentrations obtained were used in the subsequent experiments. The anti-proliferative mechanism was determined using Annexin V-FITC morphological staining and DNA fragmentation assays. The effect on tumor suppressor (p53 and PTEN) and cell cycle related genes (p21, CDK1 and Cyclin B1) were determined by QuantiGene Plex assay. Our results showed that MCF-7 cells were more sensitive to both apigenin and rutin compared to MCF-10A cells. Both cells were sensitive to tamoxifen. Apigenin and rutin synergistically enhanced tamoxifen anti-proliferative effect in MCF-7. Meanwhile rutin protects MCF-10A against the toxicity of tamoxifen. Our results indicate that the anti-proliferative mechanism of apigenin and rutin is mediated by apoptosis signals. In MCF-7 cells, both tumor suppressor (p53 and PTEN) and cell cycle related genes (p21 and CDK1) were up regulated by apigenin and rutin, contrary to tamoxifen. Apigenin and rutin induced G2/M arrest and apoptosis in MCF-7 cells through p53-dependent pathway. Both flavonoids are suggested as potential adjuvant agents to enhance tamoxifen efficacy in ERa+-breast cancer treatment.

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