Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways

Chiang, Kun‐Chun; Tsui, Ke-Hung; Chung, Li-Chuan; Yeh, Chun‐Nan; Feng, Tsui-Hsia; Chen, Wen-Tsung; Chang, Phei‐Lang; Chiang, Hou‐Yu; Juang, Horng‐Heng

doi:10.1038/srep05511

Cited by 30 publications

(41 citation statements)

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“…Taken together, our results indicated that BTG2 was stimulated by p53 in human bladder cancer cells. These results are consistent with our previous studies in the prostate carcinoma cells [18,27]. Besides p53, several reports has indicated that JNK, ERK, p38, NFκB, WNT/β-catenin, AKt/sp1/ NOx4, and Src/FAK pathways also modulate BTG2 expressions in different cancer cells [28][29][30][31][32].…”

Section: Discussionsupporting

confidence: 93%

“…Equal quantities of cell extract were resolved in 10% SDS‐polyacrylamide gel and then transferred electrophoretically to a Hybond‐P PVDF membrane at 100 volts for 2 h. The membrane was first blocked with 10% skim milk (Sigma‐Aldrich) in TBS‐T, and then probed using antisera against BTG2 , AKT (C67E7, Cell Signaling), pAKT (Ser473, Cell Signaling), GSK3 β (12456; Cell signaling), Phospho‐GSK3 β (5558; Cell signaling), mTOR (2983; Cell signaling), Phospho‐mTOR (2971; Cell signaling), p70S6K (9202; Cell signaling), Phospho‐p70S6K (9234; Cell signaling), or β ‐actin antiserum (SC‐1616, Santa Cruz Biotechnology). Proteins were visualized using the Western Lightning Chemiluminescence Reagent Plus detection system (PerkinElmer, Inc., Waltham, MA).…”

Section: Methodsmentioning

confidence: 99%

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BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

et al. 2017

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Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT‐qPCR, or reporter assays. The 3H‐thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less‐differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT‐4 cells or transient overexpression of p53 into p53‐mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site‐mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53‐induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN‐knockdown RT‐4 cells. PTEN activity inhibitor (VO‐OHpic) treatment decreased BTG2 expression in RT‐4 and PTEN‐overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

et al. 2017

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“…The exact contribution from these two mechanisms to the final outcome of enhancement of efficacy remains to be clarified. Nevertheless the implication of cisplatin-induced AR decrease is wide particularly for prostate cancer as AR has been a critical factor for cancer progression [27]. Interestingly, an early report indicated that miR-34a could serve as a ULBP2 repressor in tumors [28], which might imply miR-34a plays an opposite role in such a circumstance.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin enhances NK cells immunotherapy efficacy to suppress HCC progression via altering the androgen receptor (AR)-ULBP2 signals

Shi¹,

Lin

et al. 2016

Cancer Letters

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The aim of this study is to investigate the influence of cisplatin on the efficacy of natural killer (NK) cells immunotherapy to suppress HCC progression, and provide valuable information on better application of cisplatin in clinical settings. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of cisplatin in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection. Immunohistochemistry was performed for sample staining. We found cisplatin could enhance the efficacy of NK cell immunotherapy to better suppress HCC progression via altering the androgen receptor (AR)-UL16-binding protein 2 (ULBP2) signals both in vitro and in vivo. Mechanism dissection revealed that cisplatin could suppress AR expression via two distinct ways: increasing miR-34a-5p to suppress AR expression and altering the ubiquitination to accelerate the AR protein degradation. The suppressed AR might then function through up-regulating ULBP2, a natural-killer group 2 member D ligand, to enhance the cytotoxicity of NK cells. Together, these results indicated an unrecognized favoring effect of cisplatin in HCC treatment. By suppressing AR in HCC, cisplatin could up-regulate cytotoxicity of NK cells to better target HCC. This finding may provide a potential new approach to control HCC by combining traditional chemotherapy with immunotherapy.

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“…B-cell translocation gene 2 (BTG2) acts as a tumor suppressor gene for a number of cancers and it is stimulated by a p53-dependent pathway, which subsequently leads to the DNA damage. BTG2 gene belongs to an anti-proliferative family protein which has highly conserved domains of BTG-Box A (Y50–N71) and BTG-Box B (L97–E115) (11 –14). It has been reported that amongst the numerous molecules that are involved in diverse anti- or pro-apoptotic signaling pathways, NF-kB is one of the key factors controlling anti-apoptotic responses.…”

Section: Introductionmentioning

confidence: 99%

Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways

Zhao

Pang

2017

Braz J Med Biol Res

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Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways.

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Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways

Cited by 30 publications

References 41 publications

BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells

Cisplatin enhances NK cells immunotherapy efficacy to suppress HCC progression via altering the androgen receptor (AR)-ULBP2 signals

Iodine-131 treatment of thyroid cancer cells leads to suppression of cell proliferation followed by induction of cell apoptosis and cell cycle arrest by regulation of B-cell translocation gene 2-mediated JNK/NF-κB pathways

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