Ulyanovsk Medico-biological Journal

FUNDAMENTAL BIOLOGY AND MEDICINE

Download article

GENE EXPRESSION PROFILES DURING RADIATION-INDUCED OXIDATIVE STRESS IN CANCER CELLS WITH NORMAL AND MUTANT TP53 GENE

Y.V. Saenko, E.S. Gluschenko, A.B. Antonova, I.V. Zhivodernikov, V.P. Svekolkin, P.V. Belogubov

Ulyanovsk State University

 

The aim of the present work was to find clusters of genes whose expression is repeating the radiation-induced ROS dynamics in cancer cells with mutant and normal gene TP53. It was revealed that the expression of the gene FOS depends on the intracellular concentration of ROS in irradiated cells. In TP53 mutant cells increased in FOS gene expression is accompanied by increased in GDF15 expression, whose product, protein growth differentiation factor-15 is a repressor of the FOS protein. In cells with wild-type TP53 gene the expression of GDF15 doesn’t depend from the intracellular concentration of ROS and doesn’t coordinate with the expression of the FOS gene.

Keywords: active forms of oxygen, TP53 gene, FOS gene, GDF15 gene, DNA damage, gene expression, transcriptome, apoptosis, cancer, radiation.

 

References

  1. C-Fos as a Proapoptotic Agent in TRAIL-Induced Apoptosis in Prostate Cancer Cells / X. Zhang [et al.] // Cancer Research. – 2007. – Vol. 67, № 19. – P. 9425–9434.

  2. Characterization of 2',7'-dichlorofluorescin fluorescence in dissociated mammalian brain neurons: estimation on intracellular content of hydrogen peroxide / Y. Oyama [et al.] // Brain Res. – 1994. – Vol. 635, № 1–2. – P. 113–117.

  3. Cheng J. C. Wild-type p53 attenuates cancer cell motility by inducing growth differentiation factor-15 expression / J. C. Cheng , H. M. Chang, P. C. Leung // Endocrinology. – 2011. – Vol. 152, № 8. – P. 987–995.

  4. Differentially expressed genes in radioresis-tant nasopharyngeal cancer cells: gp96 and GDF15 / J. T.-C. Chang [et al.] // Mol. Cancer Ther. – 2007. – Vol. 6. – P. 2271–2279.

  5. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion / H. A. Coller [et al.] // Proc. Natl. Acad. Sci. U S A. – 2000. – Vol. 97, № 7. – P. 3260–3265.

  6. French L. E. The TRAIL to selective tumor death / L. E. French, J. Tschopp // Nat. Med. – 1999. – Vol. 5, № 2. – P. 146–147.

  7. Jones D. P. Radical-free biology of oxidative stress / D. P. Jones // Am. J. Physiol. Cell Physiol. – 2008. – Vol. 295. – P. 849–868.

  8. Le Caer S. Water Radiolysis: Influence of Oxide Surfaces on H2O2 Production under Ionizing Radiation / S. Le Caer // Water. – 2011. – Vol. 3. – P. 235–253.

  9. Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model / L. Zhang [et al.] // Cancer Lett. – 2007. – Vol. 251, № 1. – P. 146–157.

  10. Olivier M. TP53 mutations in human cancers: origins, consequences, and clinical use / M. Olivier, M. Hollstein, P. Hainaut // Cold Spring Harb. Perspect. Biol. – 2010. – Vol. 2, № 1.

  11. Selective activation of p53-mediated tumour suppression in high-grade tumours / M. R. Junttila [et al.] // Nature. – 2010. – № 468 (7323). – P. 567–571.

  12. Subramaniam S. Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK Pathways / S. Subramaniam, J. Strelau, K. Unsicker // J. Biol. Chem. – 2003. – Vol. 278, № 11. – P. 8904–8912.

  13. Transcriptional control of human p53-regu-lated genes / T. Riley [et al.] // Nat. Rev. Mol. Cell Biol. – 2008. – Vol. 9, № 5. – P. 402–412.

  14. Wardman P. The importance of radiation chemistry to radiation and free radical biology / P. Wardman // The British J. of Radiology. – 2009. – Vol. 82. – P. 89–104.

  15. 15. Yang J. Y. ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses / J. Y. Yang, H. E. Hamrick, P. J. Duerksen-Hughes // Carcinogenesis. – 2003. – Vol. 24, № 10. – P. 1571–1580.

 

 

Скачать статью

УДК 577.34-576.32/36:616-006.446

ИЗУЧЕНИЕ ДИНАМИКИ ТРАНСКРИПТОМА РАКОВЫХ КЛЕТОК С НОРМАЛЬНЫМ И МУТАНТНЫМ ГЕНОМ ТР53 В УСЛОВИЯХ РАДИАЦИОННО-ИНДУЦИРОВАННОГО ОКСИДАТИВНОГО СТРЕССА*

Ю.В. Саенко, Е.С. Глущенко, А.В. Антонова, И.В. Живодерников, В.П. Свеколкин, П.В. Белогубов

Ульяновский государственный университет

 

Целью работы стал поиск кластеров генов, скоординированная экспрессия которых повторяет динамику изменения внутриклеточной концентрации активных форм кислорода (АФК) после радиационного облучения в раковых клетках с мутантным и нормальным геном TP53. Выявлено, что экспрессия гена FOS зависит от внутриклеточной концентрации АФК в облученных клетках. В ТР53-мутантных клетках происходит увеличение экспрессии гена FOS, сопровождающееся увеличением экспрессии гена GDF15, продукт которого, белок ростовой фактор дифференциации-15, является репрессором белка с-FOS, тогда как в клетках с геном ТР53 дикого типа экспрессия гена GDF15 не зависит от внутриклеточной концентрации АФК и не скоординирована с экспрессией гена FOS.

Ключевые слова: активные формы кислорода, ген ТР53, ген FOS, ген GDF15, повреждение ДНК, транскриптом, апоптоз, рентгеновское излучение.

 

Литература

  1. C-Fos as a Proapoptotic Agent in TRAIL-Induced Apoptosis in Prostate Cancer Cells / X. Zhang [et al.] // Cancer Research. – 2007. – Vol. 67, № 19. – P. 9425–9434.

  2. Characterization of 2',7'-dichlorofluorescin fluorescence in dissociated mammalian brain neurons: estimation on intracellular content of hydrogen peroxide / Y. Oyama [et al.] // Brain Res. – 1994. – Vol. 635, № 1–2. – P. 113–117.

  3. Cheng J. C. Wild-type p53 attenuates cancer cell motility by inducing growth differentiation factor-15 expression / J. C. Cheng , H. M. Chang, P. C. Leung // Endocrinology. – 2011. – Vol. 152, № 8. – P. 987–995.

  4. Differentially expressed genes in radioresis-tant nasopharyngeal cancer cells: gp96 and GDF15 / J. T.-C. Chang [et al.] // Mol. Cancer Ther. – 2007. – Vol. 6. – P. 2271–2279.

  5. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion / H. A. Coller [et al.] // Proc. Natl. Acad. Sci. U S A. – 2000. – Vol. 97, № 7. – P. 3260–3265.

  6. French L. E. The TRAIL to selective tumor death / L. E. French, J. Tschopp // Nat. Med. – 1999. – Vol. 5, № 2. – P. 146–147.

  7. Jones D. P. Radical-free biology of oxidative stress / D. P. Jones // Am. J. Physiol. Cell Physiol. – 2008. – Vol. 295. – P. 849–868.

  8. Le Caer S. Water Radiolysis: Influence of Oxide Surfaces on H2O2 Production under Ionizing Radiation / S. Le Caer // Water. – 2011. – Vol. 3. – P. 235–253.

  9. Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model / L. Zhang [et al.] // Cancer Lett. – 2007. – Vol. 251, № 1. – P. 146–157.

  10. Olivier M. TP53 mutations in human cancers: origins, consequences, and clinical use / M. Olivier, M. Hollstein, P. Hainaut // Cold Spring Harb. Perspect. Biol. – 2010. – Vol. 2, № 1.

  11. Selective activation of p53-mediated tumour suppression in high-grade tumours / M. R. Junttila [et al.] // Nature. – 2010. – № 468 (7323). – P. 567–571.

  12. Subramaniam S. Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK Pathways / S. Subramaniam, J. Strelau, K. Unsicker // J. Biol. Chem. – 2003. – Vol. 278, № 11. – P. 8904–8912.

  13. Transcriptional control of human p53-regu-lated genes / T. Riley [et al.] // Nat. Rev. Mol. Cell Biol. – 2008. – Vol. 9, № 5. – P. 402–412.

  14. Wardman P. The importance of radiation chemistry to radiation and free radical biology / P. Wardman // The British J. of Radiology. – 2009. – Vol. 82. – P. 89–104.

  15. 15. Yang J. Y. ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses / J. Y. Yang, H. E. Hamrick, P. J. Duerksen-Hughes // Carcinogenesis. – 2003. – Vol. 24, № 10. – P. 1571–1580.