Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

Journal Article · Wed May 01 04:00:00 EDT 2013 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2013.02.013· OSTI ID:22285281

Krześlak, Anna; Forma, Ewa ^[1]; Chwatko, Grażyna ^[2]; Jóźwiak, Paweł; Szymczyk, Agnieszka ^[1]; Wilkosz, Jacek; Różański, Waldemar ^[3]; Bryś, Magdalena ^[1]

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1. Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland)
2. Department of Environmental Chemistry, University of Łódź, Pomorska 163, 90-236 Łódź (Poland)
3. 2nd Department of Urology, Medical University of Łódź, Pabianicka 62, 93-513 Łódź (Poland)

Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

• OSTI ID: 22285281
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 268; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CYSTEINE
GENES
HEAVY METALS
HOMEOSTASIS
HYBRIDIZATION
MESSENGER-RNA
METALLOTHIONEIN
MOLECULAR WEIGHT
NEOPLASMS
NUCLEOTIDES
PROSTATE
SPECTROMETERS
TOXICITY