Isoform-specific expression of metallothionein mRNA in the developing and adult human kidney

Mididoddi, Saibaba; McGuirt, Joan P.; Sens, Mary Ann; Todd, John H.; Sens, Donald A.

doi:10.1016/0378-4274(96)03632-6

Cited by 110 publications

(104 citation statements)

References 31 publications

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“…25 In addition to the three MT1 genes present on the array, we also selected primers for the analysis of the expression of MT1A, MT1B, MT1E, MT1F and MT2A, thus including all the MT genes ubiquitously expressed in human tissues. Informative results (based on expression level and/or reproducibility) were obtained for MT1E, MT1G, MT1X and MT2A.…”

Section: Analysis Of Mt Gene Expression In Thyroid Tumorsmentioning

confidence: 99%

“…Primers specific for the different MT isoforms, located in the divergent 5 0 and 3 0 untranslated regions, were used. 25 PCR products were subjected to direct nucleotide sequencing, and their correct identity was confirmed using BLAST software (http://www.ncbi.nlm.nih.gov/ blast). The housekeeping gene 18S was amplified using the following primers: Fw 5 0 -CGCCGCTAGAGGTGAAATTC-3 0 , Rev 5 0 -CTTTCGCTCTGGTCCGTCTT-3 0 .…”

Section: Qrt-pcrmentioning

confidence: 99%

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Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

Ferrario

Lavagni

Gariboldi

et al. 2008

Laboratory Investigation

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The molecular pathogenesis of tumors arising from the thyroid follicular epithelial cells, including papillary (PTC) and follicular thyroid carcinoma (FTC), is only partially understood, and the role of tumor suppressor genes has not yet been assessed. The metallothionein (MT) gene family encodes a class of metal-binding proteins involved in several cellular processes, and their expression is often deregulated in human tumors. Recently, downregulation of MT gene expression in PTC has been reported, suggesting a possible oncosuppressor role of this gene family in the pathogenesis of thyroid tumors. To further explore this possibility, we performed expression and functional studies. Analysis of microarray data of thyroid tumors of different histologic types showed that several MT genes were downregulated with respect to normal tissue. The microarray data were corroborated by quantitative PCR experiments, showing downregulation of MTs in PTC and FTC, but to a greater extent in papillary carcinoma. The expression of MTs was also investigated at the protein level by immunohistochemistry; the results were consistent with the microarray data, showing general downregulation in tumor samples, which was more evident in PTC. The functional consequence of MT downregulation was addressed employing an experimental model made of the PTC-derived K1 cell line in which MT1G expression is repressed by promoter methylation. Restoration of MT1G expression by cDNA transfection affected growth rate and in vivo tumorigenicity of K1 cells, indicating an oncosuppressor role for MT1G in thyroid papillary tumorigenesis. Several tumor types, differing in biological and clinical behavior, originate from the thyroid epithelial follicular cells. They include well-differentiated, indolent papillary thyroid and follicular thyroid carcinomas (PTC and FTC), as well as extremely aggressive anaplastic carcinoma. 1 Studies performed in several laboratories, including ours, have demonstrated that distinct molecular events are associated with specific tumor types. 2 FTC is characterized by the PAX8/ PPARg rearrangement and activating mutations of RAS genes. 1 PTC is associated with rearrangements involving the RET and NTRK1 tyrosine kinase receptors, 2 and the V600E BRAF-activating mutation. [3][4][5] More recently, microarray studies have identified several genes that might be important in the molecular pathogenesis and the malignant progression of thyroid cancer and could be used as diagnostic or prognostic molecular markers. These candidate genes are involved in several different processes, such as cell adhesion, cell cycle progression, mitogenic control and tumorigenesis. [6][7][8][9][10] In spite of that, the molecular pathogenesis of thyroid cancer is still incomplete; in particular, a role of tumor suppressor genes has not yet been assessed. Metallothioneins (MTs) are low-molecular weight proteins of 6-7 kDa, with high content of cysteine (30%) and complete absence of aromatic amino acids and histidine 11 capable of binding heavy metals with hig...

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Section: Analysis Of Mt Gene Expression In Thyroid Tumorsmentioning

confidence: 99%

Section: Qrt-pcrmentioning

confidence: 99%

Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

Ferrario

Lavagni

Gariboldi

et al. 2008

Laboratory Investigation

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“…As an internal quantitative control of the gene expression, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH): sense 5 0 -GTT GGA GGT CGG AGT CAA CGG A-3 0 , GAPDH, antisense 5 0 -GAG GGA TCT CGC TCC TGG AGG A-3 0 (240 bp) is used. 15 The PCR products were separated by electrophoresis on 2% agarose gels.…”

Section: Rt-pcrmentioning

confidence: 99%

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

et al. 2006

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The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factorlike domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumoros liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r ¼ 0.6594, Po0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.

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“…PCR primer oligonucleotides for the isoforms of MT were as described by Mididoddi et al (1996) and Barnes et al (2000). Hsp 70 primers were purchased from StressGen Biotechnologies Corp, Victoria, BC, Canada.…”

Section: Mt Protein Measurementmentioning

confidence: 99%

Low-Dose Cadmium Exposure Reduces Human Prostate Cell Transformation in Culture and Up-Regulates Metallothionein and MT-1G mRNA

Gaddipati

Rajeshkumar

Grove

et al. 2003

Nonlinearity in Biology, Toxicology, Medicine

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Chronic low-level exposure to environmental toxins, including cadmium (Cd), is a growing problem in the industrialized world. One promising strategy for protection from these toxins is the use of low-dose exposure of environmental chemicals to induce cell tolerance and recovery, a phenomenon known as “protective hormesis”. Hormetic [low-dose stimulatory] effects occur in a variety of systems and with a number of chemicals. Cd is a potent carcinogen in rodents and has also been linked to human lung and prostate cancers. In the present study, we have evaluated the protective effects of low and ultra-low dose, long-term Cd exposure in the normal human prostate cells, RWPE-1. Cells were exposed to low and ultra-low doses (0, 0 (S−36), 10−6, 10−7, 10−18, 10−21, 10−32, or 10−36 M) of Cd for 20 weeks followed by treatment with 10−5 M Cd for another 8 weeks. Continuous exposure of RWPE-1 cells to 10−5 M Cd results in malignant transformation. However, cells pretreated with low and ultra-low doses of Cd had delayed transformation compared with controls. In addition, the number of transformed cell mounds was lower in pretreated cells indicating that low and ultra-low dose exposure had protective effects against high-dose Cd induced carcinogenesis. The expression of metallothionein (MT), the primary Cd detoxification protein, was induced by low-dose exposure to Cd and maintained during the 20 weeks. In addition, MT-1G mRNA was up-regulated 2- to 3-fold by low-dose and ultralow-dose Cd exposures and may be the mechanism of protective hormesis in this model. MT-1G mRNA might also serve as a biological indicator of very low-dose environmental Cd exposure.

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Isoform-specific expression of metallothionein mRNA in the developing and adult human kidney

Cited by 110 publications

References 31 publications

Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

Low-Dose Cadmium Exposure Reduces Human Prostate Cell Transformation in Culture and Up-Regulates Metallothionein and MT-1G mRNA

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