TP53 gene mutations as an independent marker for urinary bladder cancer progression

Urinary bladder cancer is a common malignancy in the west and ranks 7th most cancer in this region. The primary aim of the study was to evaluate the incidence of specific RAS gene point mutations among a group of Kashmiri patients diagnosed with bladder cancer. We also explored the correlation of clinic-pathological status of the illness with these mutations.The paired tumor and adjacent normal tissue specimens of 65 consecutive patients were examined in Kashmiri population,India. The DNA preparations were evaluated for the occurrence of RAS gene mutations by PCR-SCCP and DNA sequencing.Overall somatic point mutations of all the forms of RAS genes aggregated to 21.5% . In total there were nine mutations in HRAS (three in codon 12, six in codon 61), five in NRAS (two in codon 12 and three in codon 61) and no mutation was found in KRAS gene. Overall RAS genes showed no association with any clinic-pathological parameters but when stratified alone the pattern ofHRAS mutation in this study showed a significant association with smoking in bladder tumors (p <0.05).Activation of RAS gene mutation plays a less frequent role than other genetic events in the development of the most transitional cell tumors of the bladder but contribute equally well to the development of both major tumor groups. JMS 2012;15(1):15-21

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Identification of differentially expressed proteins during human urinary bladder cancer progression

Cancer Detection and Prevention ◽

10.1016/j.cdp.2005.01.002 ◽

2005 ◽

Vol 29 (3) ◽

pp. 249-255 ◽

Cited By ~ 30

Author(s):

Ashfaque A. Memon ◽

Jong W. Chang ◽

Bong R. Oh ◽

Yung J. Yoo

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Cancer Progression ◽

Urinary Bladder Cancer ◽

Differentially Expressed ◽

Differentially Expressed Proteins ◽

Human Urinary Bladder

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CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10–ERK signaling

Cell Death and Disease ◽

10.1038/s41419-021-03819-0 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Zhengnan Huang ◽

Yilin Yan ◽

Zhen Zhu ◽

Jiakuan Liu ◽

Xiao He ◽

...

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Cancer Cell ◽

Cancer Progression ◽

Ectopic Expression ◽

Tumor Development ◽

Urinary Bladder Cancer ◽

Promoter Hypermethylation ◽

Erk Signaling ◽

Dependent Manner

AbstractThe chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.

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Deregulation of HOX B13 Expression in Urinary Bladder Cancer Progression

Current Medicinal Chemistry ◽

10.2174/092986713805076658 ◽

2013 ◽

Vol 20 (6) ◽

pp. 833-839 ◽

Cited By ~ 3

Author(s):

L. Marra ◽

M. Cantile ◽

G. Scognamiglio ◽

L. Marra ◽

S. Perdona ◽

...

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Cancer Progression ◽

Urinary Bladder Cancer

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CHEK2 gene mutations, CYP1B1 gene 355T/T polymorphism, and HIV infection approached as urinary bladder cancer predisposing factors

Central European Journal of Urology ◽

10.5173/ceju.2010.04.art2 ◽

2010 ◽

Vol 63 ◽

pp. 176-181

Author(s):

Monika Banaszkiewicz ◽

Maria Constantinou ◽

Michał Pietrusiński ◽

Adam Jędrzejczyk ◽

Marek Rożniecki ◽

...

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Hiv Infection ◽

Gene Mutations ◽

Urinary Bladder Cancer ◽

Predisposing Factors ◽

Chek2 Gene ◽

Cyp1b1 Gene

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Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells

Mutagenesis ◽

10.1093/mutage/geaa021 ◽

2020 ◽

Author(s):

Ana Paula Braga Lima ◽

Tamires Cunha Almeida ◽

Tatiane Martins Barcelos Barros ◽

Lorrana Cachuite Mendes Rocha ◽

Camila Carriao Machado Garcia ◽

...

Keyword(s):

Bladder Cancer ◽

Urinary Bladder ◽

Cancer Cells ◽

Bladder Tumour ◽

Urinary Bladder Cancer ◽

Tp53 Gene ◽

Tumour Cells ◽

Wild Type ◽

Tp53 Status

Abstract The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

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