WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells

Cuddihy, Andrew; Jalali, Farid; Coackley, Carla; Bristow, Robert G.

doi:10.1158/1535-7163.mct-07-0471

Cited by 18 publications

(18 citation statements)

References 72 publications

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“…Thus X-ray irradiation may activate apoptotic and antiapoptotic functions (28)(29)(30). The expression of p53 regulates several target genes, including p21WAF1, Bax, and PUMA; moreover, it may alter the biological behavior and sensitivity of tumor cells to cancer therapy and may be very important in acquiring resistance to ionizing radiation (31,32). In our IPA analysis of microarray data, we found that TP53I3 was involved in the p53 network.…”

Section: Discussionmentioning

confidence: 72%

Differential Gene Expression Profiles of Radioresistant Non–Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

Lee¹,

Oh²,

Yoon³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionmentioning

confidence: 72%

Differential Gene Expression Profiles of Radioresistant Non–Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

Lee¹,

Oh²,

Yoon³

et al. 2010

International Journal of Radiation Oncology*Biology*Physics

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“…FITC-conjugated anti-BrdUrd antibody-labeled (BD Biosciences) and propidium iodide (PI)-stained cells were analyzed with a FACSCalibur flow cytometer and CellQuest Pro software (BD Biosciences) as previously described (27). GMO5757 cell cycle profiles were obtained using PI staining.…”

Section: Cell Cycle Analysis and Fluorescence-activated Cell Sortingmentioning

confidence: 99%

“…For all assays, cells were fixed and stained in 1% methylene blue in 50% ethanol 10 to 15 days later. Surviving clones with >50 cells were scored under a light microscope, and resulting survival was calculated as previously described (27,28). For apoptosis assays, H1299 cells (or Rat-1/myc controls) were treated with 0.5 μg/mL MMC for 1 hour or with 2 or 10 Gy IR at 48 hours after siRNA transfection and assessed for sub-G 1 populations by flow cytometry or nuclear apoptotic bodies, as previously described (21).…”

Section: Clonogenic Survival and Apoptosis Assaysmentioning

confidence: 99%

Tumor Cell Kill by c-MYC Depletion: Role of MYC-Regulated Genes that Control DNA Double-Strand Break Repair

et al. 2010

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MYC regulates a myriad of genes controlling cell proliferation, metabolism, differentiation, and apoptosis. MYC also controls the expression of DNA double-strand break (DSB) repair genes and therefore may be a potential target for anticancer therapy to sensitize cancer cells to DNA damage or prevent genetic instability. In this report, we studied whether MYC binds to DSB repair gene promoters and modulates cell survival in response to DNA-damaging agents. Chromatin immunoprecipitation studies showed that MYC associates with several DSB repair gene promoters including Rad51, Rad51B, Rad51C, XRCC2, Rad50, BRCA1, BRCA2, DNA-PKcs, XRCC4, Ku70, and DNA ligase IV. Endogenous MYC protein expression was associated with increased RAD51 and KU70 protein expression of a panel of cancer cell lines of varying histopathology. Induction of MYC in G 0 -G 1 and S-G 2 -M cells resulted in upregulation of Rad51 gene expression. MYC knockdown using small interfering RNA (siRNA) led to decreased RAD51 expression but minimal effects on homologous recombination based on a flow cytometry direct repeat green fluorescent protein assay. siRNA to MYC resulted in tumor cell kill in DU145 and H1299 cell lines in a manner independent of apoptosis. However, MYC-dependent changes in DSB repair protein expression were not sufficient to sensitize cells to mitomycin C or ionizing radiation, two agents selectively toxic to DSB repair-deficient cells. Our results suggest that anti-MYC agents may target cells to prevent genetic instability but would not lead to differential radiosensitization or chemosensitization. Cancer Res; 70(21); 8748-59. ©2010 AACR.

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“…Thus, we hypothesize that a low dose of GA can enhance the ability of I 131 to regulate Bcl-2 and Bax expression, which may promote apoptosis in A549/DDP cells. Other previous studies of lung cancer have found that wild-type P53 can promote tumor cell apoptosis (46,47), increasing the chemosensitivity of tumor cells (48,49). However, mutant P53 can promote chemotherapeutic tolerance in tumor cells via several factors, such as decreased pro-apoptotic capacity, increased DNA repair function (50,51) and upregulated P-gP expression (9,52).…”

mentioning

confidence: 94%

Role of gambogic acid and NaI131 in A549/DDP cells

et al. 2016

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Abstract. Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI 131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI 131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI 131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI 131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI 131 and GA intervention. NaI 131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI 131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

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WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells

Cited by 18 publications

References 72 publications

Differential Gene Expression Profiles of Radioresistant Non–Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

Differential Gene Expression Profiles of Radioresistant Non–Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

Tumor Cell Kill by c-MYC Depletion: Role of MYC-Regulated Genes that Control DNA Double-Strand Break Repair

Role of gambogic acid and NaI131 in A549/DDP cells

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