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

Autor: Merlos Rodrigo MA; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Dostalova S; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Buchtelova H; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Strmiska V; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Michalek P; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Krizkova S; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Vicha A; Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, CZ-150 06 Prague 5, Czech Republic., Jencova P; Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, CZ-150 06 Prague 5, Czech Republic., Eckschlager T; Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, CZ-150 06 Prague 5, Czech Republic., Stiborova M; Department of Biochemistry, Faculty of Science, Charles University, CZ-128 40 Prague 2, Czech Republic., Heger Z; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic., Adam V; Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.; Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic.
Jazyk: angličtina
Zdroj: Oncotarget [Oncotarget] 2017 Dec 16; Vol. 9 (4), pp. 4427-4439. Date of Electronic Publication: 2017 Dec 16 (Print Publication: 2018).
DOI: 10.18632/oncotarget.23333
Abstrakt: 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 μg/ml), indicating its multipurpose biological significance.
Competing Interests: CONFLICTS OF INTEREST The authors declare that no competing interests exist.
Databáze: MEDLINE