Overexpression of MDM‐2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines

Cheng, Y; Li, Yuling; Wu, Jeng Dau; Long, Shih-Bin; Tzai, Tzong-Shin; Tzeng, Ching‐Cherng; Lai, Ming‐Derg

doi:10.1002/mc.2940130307

Cited by 37 publications

(24 citation statements)

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“…The human urinary bladder carcinoma J82 cell line hosts wild-type ras genes and is not tumorigenic to immunedeficient mice (15,16,21). In our studies, introduction of the oncogenic H-ras gene into J82 cells promoted cells to acquire the tumorigenic ability to develop xenograft tumors in immune-deficient mice; however, it was also accompanied by the novel proapoptotic property for FR901228 and TSA to induce selective apoptosis.…”

Section: Discussionmentioning

confidence: 58%

“…J82 cells host the mutant p53 gene (15), and the mutant p53 protein was progressively and substantially reduced in J82 and J82-Ras cells undergoing FR901228-induced growth arrest followed by apoptosis. It has been suggested that FR901228 induces a novel p53-related feedback activity that results in depletion of mutant p53 protein in association with increased cytotoxicity of FR901228 to tumor cells (40,41).…”

Section: Discussionmentioning

confidence: 97%

“…The J82 human urinary bladder transitional carcinoma cell line hosts wild-type ras and the inactive mutant Rb and p53 genes with deletion of the pTEN gene (15,16). Expression of oncogenic H-Ras promoted J82 cells to acquire tumorigenicity, mimicking an acquisition of H-ras gene activation in tumor development.…”

Section: Introductionmentioning

confidence: 99%

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Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Choudhary

Wang

2007

Molecular Cancer Therapeutics

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 97%

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Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Choudhary

Wang

2007

Molecular Cancer Therapeutics

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“…It is plausible that tumour cells in which high levels of MDM2 suppress p53 may allow E1B-deleted adenovirus replication. BFTC-905 cells have been shown to overexpress MDM2 mRNA (Cheng et al, 1995), which may explain in part why Ad5WS1 at high doses caused CPE, albeit to a very small extent, in bladder cancer cells harbouring wild-type p53. Further analysis of the p53 pathway in bladder cancer cells may answer part of this question.…”

Section: Discussionmentioning

confidence: 99%

Gene therapy for bladder cancer using E1B-55 kD-deleted adenovirus in combination with adenoviral vector encoding plasminogen kringles 1–5

Hsieh

Lai

et al. 2003

Br J Cancer

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Mutations or loss of heterozygosity of p53 are detected in approximately 50% of bladder cancers. E1B-55 kD-deleted adenovirus has been shown to kill tumour cells with defective p53 function while sparing normal cells. Here, we examined the cytolytic effect and replication of E1B-55 kD-deleted adenovirus, designated Ad5WS1, on human bladder cancer cell lines with various p53 status. Ad5WS1 caused more severe cytolytic effect and replicated more efficiently in J82 and TCC-SUP bladder cancer cells carrying mutant p53 compared with TSGH-8301 and BFTC-905 bladder cancer cells retaining wild-type p53. Introduction of dominant negative p53 into BFTC-905 cells rendered them more susceptible to Ad5WS1-induced cytolysis. Furthermore, cells susceptible to lysis caused by Ad5WS1 were not attributable to their greater infectability by adenovirus. Finally, Ad5WS1 suppressed the growth of TCC-SUP bladder tumour xenografts, which could be augmented when combined with replication-defective adenoviral vector encoding kringles 1 -5 of plasminogen (K1 -5), an angiogenic inhibitor. Taken together, our results show that E1B-55 kD-deleted adenovirus replicates and hence lyses bladder cancer cells with mutant p53 much more efficient than those with wild-type p53. Thus, E1B-deleted adenovirus may have therapeutic potential, especially in combination with adenoviral vector expressing K1 -5, for the treatment of bladder cancer.

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“…These levels were consistent with those recorded after overexpression of p53 through DNA damage or apoptotic insult . Although allelic exclusion or mutations in MDM2 have been associated with abnormalities in p53 in numerous cell lines (Cheng et al, 1995), it appears that differential MDM2 expression was not responsible for the differences in apoptotic response demonstrated by U87-Lux.8 and U87-175.4.…”

Section: Expression Of P53 Target Genes After Ad-p53 Infectionmentioning

confidence: 92%

Introduction of mutant p53 into a wild-type p53-expressing glioma cell line confers sensitivity to Ad-p53-induced apoptosis

Cerrato¹,

Yung²,

Liu³

2001

Neuro-Oncol

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Neuro-Oncology nA P R I L 2 0 0 1 113 Transient expression of the tumor suppressor gene p53 via adenoviral-mediated gene transfer induces apoptosis in glioma cells expressing mutant p53, while causing cell cycle arrest in cells with wild-type p53. To determine whether a change in p53 status of a wild-type p53-expressing cell line such as U-87 MG would alter its apoptotic resistant phenotype in response to Ad-p53 infection, we generated cell lines U-87-175.4 and U-87-175.13 via retroviral-mediated gene transfer of the p53 (175H) mutant into the U-87 MG parental line. Control cell lines U-87-Lux.6 and U-87-Lux.8 were also generated and express the reporter gene luciferase. Both U-87-175.4 and U-87-175.13, but not control cell lines, exhibited morphology characteristic of apoptosis after Ad-p53 infection. Furthermore, expression of other p53 mutants (248W, 273H) in U-87 MG also sensitized cells to Adp53-induced apoptosis. Apoptosis was con rmed by TUNEL and cell cycle analysis. Several p53 response genes were examined in cells infected with Ad-p53, and among these, BCL2, p21 WAF1/CIP1 , CPP32/caspase 3, and PARP showed differences in expression between U87-175 and U87-Lux cell lines. Taken together, our data demonstrate that the introduction of p53 mutants in U-87 MG promotes an apoptotic response in association with adenoviral-mediated wild-type p53 gene transfer. These results underscore the importance of glioma p53 genotype for predicting tumor response to p53-based gene therapy. Neuro-Oncology 3, 113-122, 2001 (Posted to NeuroOncology [serial online], Doc. 00-043, February 20, 2001 The p53 tumor suppressor gene is a nuclear phosphoprotein that transcriptionally regulates the expression of a number of target genes including p21 WAF1/CIP1 (el-Deiry et al., 1993), GADD45 (Hollander et al., 1993), BAX (Miyashita and Reed, 1995), and FAS/APO1 (OwenSchaub et al., 1995). In normal cells, the p53 protein is expressed at low levels and has a short half-life due to a rapid turnover rate mediated by ubiquitination and proteolysis. Upon exposure to a number of stressful stimuli, including DNA-damaging agents and hypoxia (Carmeliet et al., 1998), the p53 protein is stabilized and, in turn, regulates biological functions including cell cycle arrest (elDeiry et al., 1994), apoptosis (Liu et al., 1995), senescence (Sugrue et al., 1997), differentiation, and antiangiogenesis (Dameron et al., 1994). However, p53 function is often deregulated or impaired after the occurrence of mutations or deletions resulting from neoplastic transformation.Astrocytomas and glioblastomas are the most frequently occurring CNS tumors of neuro-epithelial origin and the most challenging brain tumors to treat. In more than 30% of astrocytomas, mutations exist in the p53 tumor suppressor gene whereby inactivation occurs through missense mutation or loss of heterozygosity (Van Meir et al., 1994) Abbreviations used are as follows: AdDE1, replication defective adenovirus; Ad-p53, wild-type p53 adenovirus; MOI, multiplicity of infection; PBS, phosphate-...

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Overexpression of MDM‐2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines

Cited by 37 publications

References 36 publications

Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells

Gene therapy for bladder cancer using E1B-55 kD-deleted adenovirus in combination with adenoviral vector encoding plasminogen kringles 1–5

Introduction of mutant <I>p53</I> into a wild-type <I>p53</I>-expressing glioma cell line confers sensitivity to Ad-p53-induced apoptosis

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