Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer

Miyake, Hideaki; Hanada, Norihisa; Nakamura, Hideo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hara, Isao; Eto, Hiroshi; Gohji, Kazuo; Arakawa, Soichi; Kamidono, Sadao; Saya, Hideyuki

doi:10.1038/sj.onc.1201602

Cited by 110 publications

(88 citation statements)

References 24 publications

(33 reference statements)

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“…They are multifaceted and complex, and can include the involvement of membrane-associated e ux pumps, the up-regulation of cellular detoxifying thiols, enhanced DNA repair activity and the inhibition of apoptotic pathways (Ishikawa et al, 1994;Andrews et al, 1985;Lai et al, 1988Lai et al, , 1989Chu, 1994;Chu and Chang, 1990;Zhen et al, 1992;Miyake et al, 1998;Citro et al, 1998). In many malignancies, drug resistance is acquired through prolonged and repeated exposure to a chemotherapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

et al. 2000

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A major obstacle in the systemic treatment of advanced malignant melanoma is its intrinsic resistance to conventionally used chemotherapeutic agents. In order to investigate the mechanisms of this intrinsic resistance, we have previously utilized retroviral insertional mutagenesis on an early-stage, drug sensitive human melanoma cell line (WM35) to establish mutated cell lines that exhibited increased resistance to cis-diamminedichloroplatinum(II) (CDDP). Here, we demonstrate that this increased resistance to CDDP is mediated by the over-expression of tyrosinase-related protein-2 (TYRP2), an enzyme that normally functions in the biosynthesis of the pigment, melanin. Northern and Western blot analyses revealed that the expression of TYRP2 in the virally-derived cell lines as well as in a panel of human melanoma cell lines positively correlated with their levels of resistance to CDDP. Furthermore, enforced expression of TYRP2 in WM35 cells by transfection elevated their resistance to CDDP. The increased CDDP resistance in the virally-derived clones and TYRP2 transfectants was accompanied by a reduction in CDDP-induced apoptosis. Interestingly, the virally-derived CDDP-resistant clones also showed cross resistance to carboplatin and methotrexate, but not taxol, suggesting that TYRP2 over-expression may confer resistance speci®cally to DNA damaging agents.Overall, these results demonstrate a novel mechanism of drug resistance in human melanoma cells that is mediated by the over-expression of TYRP2. Since TYRP2 is expressed only in cells of melanocytic lineage, this may represent the ®rst report of a lineage-speci®c mechanism of drug resistance. In summary, these ®ndings suggest a signi®cant role for TYRP2 in the intrinsic drug resistance phenotype of human melanoma cells and may have important implications in the development of chemosensitization strategies for the clinical management of this disease. Oncogene (2000) 19, 395 ± 402.

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Section: Discussionmentioning

confidence: 99%

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

et al. 2000

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“…Adenoviruses were propagated and titrated in the permissive 293 cell line. Viral infection titers were determined as described previously (24). Cells (3 ϫ 10 5 ) were plated 24 h before infection and cultured for the indicated times with each adenovirus at a multiplicity of infection of 100 plaque-forming units per cell.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Arima

Nitta

Kuninaka

et al. 2005

Journal of Biological Chemistry

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139

145

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The tumor suppressor p53 functions as a transcriptional activator to induce cell cycle arrest and apoptosis in response to DNA damage. Although p53 was also shown to mediate apoptosis in a manner independent of its transactivation activity, the mechanism and conditions that trigger such cell death have remained largely unknown. We have now shown that inhibition of RNA polymerase II-mediated transcription by ␣-amanitin or RNA interference induced p53-dependent apoptosis. Inhibition of pol II-mediated transcription resulted in down-regulation of p21 Cip1 , which was caused by both transcriptional suppression and protein degradation, despite eliciting p53 accumulation, allowing the cells to progress into S phase and then to undergo apoptosis. This cell death did not require the transcription of p53 target genes and was preceded by translocation of the accumulated p53 to mitochondria. Our data thus suggested that blockade of pol II-mediated transcription induced p53 accumulation in mitochondria and was the critical factor for eliciting p53-dependent but transcription-independent apoptosis.

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“…However, development of acquired resistance is likely to be accompanied by an altered pattern of gene expression in the cell. Changes in cDDP sensitivity have been reported in cells molecularly engineered to over-express a variety of genes including MYC, RASA1, FOS, JUN (5), ERBA2 (6, 7), MT2A11 (8), TP53 (5), BCL2 (9), and MSH2 (10). However, whether any of these play a role in naturally occurring acquired resistance is uncertain.…”

Section: Cddp-resistancementioning

confidence: 99%

Using mRNA expression profiling to determine anticancer drug efficacy

et al. 2001

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Pharmacogenomics is a fast‐growing field of investigations that aims to further elucidate the inherited nature of interindividual differences in drug disposition and effects, with the ultimate goal of providing a stronger scientific basis for selecting the optimal drug therapy. Providing the right drug for the right patient is an important problem in the treatment of cancer. This is mainly due to the lack of information about the sensitivity of the tumor for a specific treatment modality, such as either chemotherapy or radiation treatment. This presentation highlights two approaches to identify responsiveness to treatment. Both approaches are based on the identification of expression profiles. The first approach concentrates on drug resistance and the second on the signaling pathways leading up to the death of the cell. Both approaches provide expression profiles; however, the more dynamic expression profiling as used to determine the signaling in damage cells promises to be a better determinant for the pharmacogenomic changes in expression profiles and, consequently, a potential better determinant for drug efficacy. Cytometry 47:66–71, 2002. © 2001 Wiley‐Liss, Inc.

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Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer

Cited by 110 publications

References 24 publications

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

Transcriptional Blockade Induces p53-dependent Apoptosis Associated with Translocation of p53 to Mitochondria

Using mRNA expression profiling to determine anticancer drug efficacy

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