Publication detail

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

MERLOS RODRIGO, M. DOSTÁLOVÁ, S. BUCHTELOVÁ, H. STRMISKA, V. MICHÁLEK, P. KŘÍŽKOVÁ, S. VÍCHA, A. JENČOVÁ, P. ECKSCHLAGER, T. STIBOROVÁ, M. HEGER, Z. ADAM, V.

Original Title

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

Type

journal article in Web of Science

Language

English

Original Abstract

Human metallothionein-3 (hMT-3), also known as growth inhibitory factor, is predominantly expressed in the central nervous system. hMT-3 is presumed to participate in the processes of heavy metal detoxification, regulation of metabolism and protection against oxidative damage of free radicals in the central nervous system; thus, it could play important neuromodulatory and neuroprotective roles. However, the primary functions of hMT-3 and the mechanism underlying its multiple functions in neuroblastoma have not been elucidated so far. First, we confirmed relatively high expression of hMT-3 encoding mRNA in biopsies (n = 23) from high-risk neuroblastoma subjects. Therefore, we focused on investigation of the impact of hMT-3 up-regulation in N-Myc amplifying neuroblastoma cells. The differentially up-regulated genes involved in biological pathways related to cellular senescence and cell cycle were identified using electrochemical microarray with consequent bioinformatic processing. Further, as experimental verification of microarray data, the cytotoxicity of the cisplatin (CDDP) was examined in hMT-3 and mock cells by MTT and clonogenic assays. Overall, our data strongly suggest that up-regulation of hMT-3 positively correlates with the genes involved in oncogene-induced senescence (CDKN2B and ANAPC5) or apoptosis (CASP4). Moreover, we identified a significant increase in chemoresistance to cisplatin (CDDP) due to hMT-3 up-regulation (24IC(50): 7.5 vs. 19.8 mu g/ml), indicating its multipurpose biological significance.

Keywords

apoptosis; cisplatin; chemoresistance; metallothionein; oncogene-induced senescence

Authors

MERLOS RODRIGO, M.; DOSTÁLOVÁ, S.; BUCHTELOVÁ, H.; STRMISKA, V.; MICHÁLEK, P.; KŘÍŽKOVÁ, S.; VÍCHA, A.; JENČOVÁ, P.; ECKSCHLAGER, T.; STIBOROVÁ, M.; HEGER, Z.; ADAM, V.

Released

12. 1. 2018

Publisher

Impact Journals

ISBN

1949-2553

Periodical

Oncotarget

Year of study

9

Number

4

State

United States of America

Pages from

4427

Pages to

4439

Pages count

13

URL

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=23333&path[]=73538

Full text in the Digital Library

http://hdl.handle.net/11012/72413

BibTex

@article{BUT145110,
  author="MERLOS RODRIGO, M. and DOSTÁLOVÁ, S. and BUCHTELOVÁ, H. and STRMISKA, V. and MICHÁLEK, P. and KŘÍŽKOVÁ, S. and VÍCHA, A. and JENČOVÁ, P. and ECKSCHLAGER, T. and STIBOROVÁ, M. and HEGER, Z. and ADAM, V.",
  title="Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin",
  journal="Oncotarget",
  year="2018",
  volume="9",
  number="4",
  pages="4427--4439",
  doi="10.18632/oncotarget.23333",
  issn="1949-2553",
  url="http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=23333&path[]=73538"
}