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

Krześlak, Anna; Forma, Ewa; Chwatko, Grażyna; Jóźwiak, Paweł; Szymczyk, Agnieszka; Wilkosz, Jacek; Różański, Waldemar; Bryś, Magdalena

doi:10.1016/j.taap.2013.02.013

Cited by 34 publications

(53 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an in vitro study it could be shown that MT-2A induces MMP-9 up-regulation through the activation of NFκB and Ap-1 signalling pathways, which can facilitate the migration and invasion of breast cancer cells [17]. Earlier, the same SNP had been shown to be linked with higher MT2A mRNA expression in prostate cancer tissue [3].…”

Section: Pcr and Rt-pcrmentioning

confidence: 99%

“…These proteins are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions [2] and their main functions include metal ions detoxification of the organism [3] and scavenging free radicals to protect cells against oxidative stress [4]. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic process (Fig.…”

Section: Metallothioneinsmentioning

confidence: 99%

“…These occur in tissues of kidney, liver, intestine and pancreas. MT-1A, E, X and MT-2A isoforms were found in normal prostate tissue [3]. MT-2A isoform is also connected with the proliferative activity of human prostate cancer cells [16] and breast cancer [17].…”

Section: Isoforms Of Metallothioneinsmentioning

confidence: 99%

“…Besides, metallothionein 2A's polymorphs were studied for their association with the risk for a variety of diseases such as prostate cancer, atherosclerosis, stroke and diabetes [3,18]. is found mainly in the brain, but it is expressed also in heart, kidney, and stomach in trace amounts [19].…”

Section: Isoforms Of Metallothioneinsmentioning

confidence: 99%

See 3 more Smart Citations

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Microarray analysis of metallothioneins in human diseases AbstractMetallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. 3The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adiposetissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review. List of abbreviations:HCC -hepatocellular carcinoma, HFD -high fat diet, MMP -matrix metalloproteinase, MT -metallothionein, MTF -metal transcription factor, MRE -metal responsive element, ROS -reactive oxygen species.

show abstract

Section: Pcr and Rt-pcrmentioning

confidence: 99%

Section: Metallothioneinsmentioning

confidence: 99%

Section: Isoforms Of Metallothioneinsmentioning

confidence: 99%

Section: Isoforms Of Metallothioneinsmentioning

confidence: 99%

See 2 more Smart Citations

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

show abstract

“…However, so far, there are very limited data concerning the effects of polymorphisms of MTs on Pb body burden and toxicity [17,18,19,20], which reinforces the need for further studies for a better comprehension of the interactions between the genetic variations and Pb exposure. Thus, taking into consideration the important role of MTs in the metal metabolism and the lack of information concerning the effects of polymorphisms of MT genes and Pb exposure, this study aimed to evaluate the influence of the single nucleotide polymorphism of MT2A , rs10636, C→G, on blood Pb concentrations in workers chronically exposed to the metal.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal

Fernandes

Martins

Oliveira

et al. 2015

Public Health Genomics

View full text Add to dashboard Cite

Lead (Pb) is a metal that accumulates in the human body, inducing several adverse health effects. One of the proteins responsible for the distribution of metal in the body is metallothionein (MT), which is expressed by different genes, and it is supposed that genetic variation in the genes that encode MTs may affect the Pb body burden. The present study aimed to evaluate the genetic effects of the polymorphism of MT2A (single nucleotide polymorphism rs10636; C→G) on blood Pb levels (BLL) of workers from car battery factories who are chronically exposed to the metal. In total, 221 men participated in the study; genomic DNA from whole blood was extracted, and genotyping of MT2A was performed by TaqMan assays; BLL were quantified by inductively coupled plasma mass spectrometry (ICP-MS). BLL were 25 ± 14 µg/dl (range 1.9-68); BLL were positively correlated with duration of work and smoking status. Individuals who carried at least one C allele had higher BLL than those with the GG genotype (β = -0.45; p = 0.025, multivariable linear regression analyses). Taken together, our data support the hypothesis that polymorphisms in genes related to the transport of Pb, such as MTs, may modulate the concentrations of the metal in the body and, consequently, adverse health effects induced by Pb exposure.

show abstract

Levels of heavy metals and their binding protein metallothionein in type 2 diabetics with kidney disease

Raudenská

Dvořáková

Pácal

et al. 2017

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Hyperglycemia, a major metabolic disturbance present in diabetes, promotes oxidative stress. Activation of antioxidant defense is an important mechanism to prevent cell damage. Levels of heavy metals and their binding proteins can contribute to oxidative stress. Antiradical capacity and levels of metallothionein (MT), metals (zinc and copper), and selected antioxidants (bilirubin, cysteine, and glutathione) were determined in 70 type 2 diabetes mellitus (T2DM) subjects and 80 healthy subjects of Caucasian origin. Single nucleotide polymorphism (rs28366003) in MT gene was detected. Antiradical capacity, conjugated bilirubin, and copper were significantly increased in diabetics, whereas MT and glutathione were decreased. Genotype AA of rs28366003 was associated with higher zinc levels in the diabetic group. The studied parameters were not influenced by renal function. This is the first study comprehensively investigating differences in MT and metals relevant to oxidative stress in T2DM. Ascertained differences indicate increased oxidative stress in T2DM accompanied by abnormalities in non-enzymatic antioxidant defense systems.

show abstract

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

Cited by 34 publications

References 44 publications

Microarray analysis of metallothioneins in human diseases—A review

Microarray analysis of metallothioneins in human diseases—A review

Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal

Levels of heavy metals and their binding protein metallothionein in type 2 diabetics with kidney disease

Contact Info

Product

Resources

About