C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

André O. von Bueren, Christoph Oehler, Tarek Shalaby, Katja von Hoff, Martin Pruschy, Burkhardt Seifert, Nicolas U. Gerber, Monika Warmuth-Metz, Duncan Stearns, Charles G Eberhart, Rolf D. Kortmann, Stefan Rutkowski, Michael A. Grotzer

Research output: Contribution to journalArticle

Abstract

Background: To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB).Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging.Results: In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively).Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment.

Original languageEnglish (US)
Article number74
JournalBMC Cancer
Volume11
DOIs
StatePublished - Feb 16 2011

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Medulloblastoma
Radiotherapy
Residual Neoplasm
Drug Therapy
Messenger RNA
Tetrazolium Salts
Radiation Tolerance
Etoposide
Nonparametric Statistics
Radio
Heterografts
Paraffin
Formaldehyde
Cisplatin
Neoplasms
Cell Cycle
Cell Death
Western Blotting
Apoptosis
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

von Bueren, A. O., Oehler, C., Shalaby, T., von Hoff, K., Pruschy, M., Seifert, B., ... Grotzer, M. A. (2011). C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients. BMC Cancer, 11, [74]. https://doi.org/10.1186/1471-2407-11-74

C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients. / von Bueren, André O.; Oehler, Christoph; Shalaby, Tarek; von Hoff, Katja; Pruschy, Martin; Seifert, Burkhardt; Gerber, Nicolas U.; Warmuth-Metz, Monika; Stearns, Duncan; Eberhart, Charles G; Kortmann, Rolf D.; Rutkowski, Stefan; Grotzer, Michael A.

In: BMC Cancer, Vol. 11, 74, 16.02.2011.

Research output: Contribution to journalArticle

von Bueren, AO, Oehler, C, Shalaby, T, von Hoff, K, Pruschy, M, Seifert, B, Gerber, NU, Warmuth-Metz, M, Stearns, D, Eberhart, CG, Kortmann, RD, Rutkowski, S & Grotzer, MA 2011, 'C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients', BMC Cancer, vol. 11, 74. https://doi.org/10.1186/1471-2407-11-74
von Bueren, André O. ; Oehler, Christoph ; Shalaby, Tarek ; von Hoff, Katja ; Pruschy, Martin ; Seifert, Burkhardt ; Gerber, Nicolas U. ; Warmuth-Metz, Monika ; Stearns, Duncan ; Eberhart, Charles G ; Kortmann, Rolf D. ; Rutkowski, Stefan ; Grotzer, Michael A. / C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients. In: BMC Cancer. 2011 ; Vol. 11.
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abstract = "Background: To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB).Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging.Results: In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95{\%} CI 0.008-30.0 and p = 0.67, ratio 1.8, 95{\%} CI 0.14-23.5, respectively).Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment.",
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T1 - C-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

AU - von Bueren, André O.

AU - Oehler, Christoph

AU - Shalaby, Tarek

AU - von Hoff, Katja

AU - Pruschy, Martin

AU - Seifert, Burkhardt

AU - Gerber, Nicolas U.

AU - Warmuth-Metz, Monika

AU - Stearns, Duncan

AU - Eberhart, Charles G

AU - Kortmann, Rolf D.

AU - Rutkowski, Stefan

AU - Grotzer, Michael A.

PY - 2011/2/16

Y1 - 2011/2/16

N2 - Background: To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB).Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging.Results: In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively).Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment.

AB - Background: To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB).Methods: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging.Results: In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively).Conclusions: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment.

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