Metallothionein expression in human neoplasia

@article{Theocharis2004MetallothioneinEI,
  title={Metallothionein expression in human neoplasia},
  author={Stamos Theocharis and Alexandra P. Margeli and Jerzy Klijanienko and Gregorios Kouraklis},
  journal={Histopathology},
  year={2004},
  volume={45}
}
The metallothionein family is a class of low‐molecular‐weight, cysteine‐rich proteins with high affinity for metal ions. Four major isoforms (metallothionein‐1, ‐2, ‐3, and ‐4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the… 

Metallothionein isoforms as double agents - Their roles in carcinogenesis, cancer progression and chemoresistance.

Metallothioneins and zinc in cancer diagnosis and therapy

The structure and function of MTs are strongly dependent on Zn2+ redox state and its binding to proteins and their importance for chemoresistance is also mentioned.

Molecular functions of metallothionein and its role in hematological malignancies

The author summarizes the current understanding of the molecular functions of MT for tumor cell growth and drug resistance, which are regulated through intracellular metal ion modulation and free radical scavenging.

Metallothioneins in Drug Resistance

The importance of inflammation, hormone response, antiapoptotic and zinc-dependent transcription factor function, and zinc regulation in cellular resistance to toxins, coupled with understanding of how MT influences them, sets the stage for rational therapeutic targeting of MT to enhance cancer treatment while sparing normal tissues.

Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas.

Frequent downregulation of MT1M in human HCC may contribute to liver tumorigenesis by increasing cellular NF-κB activity.

Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma

Analysis of microarray data of thyroid tumors of different histologic types showed that several metallothionein genes were downregulated with respect to normal tissue, showing general downregulation in tumor samples, which was more evident in PTC and FTC than in papillary carcinoma.

The role of metallothionein in oncogenesis and cancer prognosis.

Positive and negative regulators of the metallothionein gene (review).

The present review focuses on PU.1 and several other negative regulators of this gene, including PZ120, DNA methyltransferase 3a with Mbd3 and Brg1 complex, CCAAT enhancer binding protein α and Ku protein, and describes the suppression of the MT genes through these transcription factors.
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References

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Metallothionein: a multifunctional protein from toxicity to cancer.

The involvement of metallothionein in defense mechanisms to toxicity and in carcinogenicity is discussed.

Metallothionein expression in human breast cancer.

The assessment of metallothionein expression in human breast cancer appears to provide prognostic information and may have important implications for understanding its development.

Prognostic significance of metallothionein in human gastrointestinal cancer.

Overexpression of MT in intestinal tissue of colorectal cancer patients is a prognostic marker for a poor overall survival, and in gastric cancer, MT expression in the gastric mucosa is not of prognostic significance, which emphasizes the clinical relevance of this multifunctional metalloprotein in coloreCTal carcinogenesis and therapy.

Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis

In conclusion, MT expression as well as the product of MT and GSH were associated with histological grade of primary ovarian carcinomas, suggesting that high expression of sulfhydryl factors might facilitate survival and progression of low‐grade ovarian cancer cells.

OVER‐EXPRESSION OF METALLOTHIONEIN AND DRUG‐RESISTANCE IN BLADDER CANCER

  • T. SaikaT. Tsushima H. Ohmori
  • Biology, Medicine
    International journal of urology : official journal of the Japanese Urological Association
  • 1994
A correlation exists between MT expression and tumor differentiation and repetitive and continuous administration of anti‐cancer drugs results in increased MT expression in bladder cancer cells, which may therefore be one of the mechanisms by which urothelial tumors acquire resistance to anti-cancer drugs.

The prognostic significance of immunohistochemically detectable metallothionein in primary breast carcinomas

In univariate analysis of survival data, MT overexpression was a predictor of poor overall survival in the entire group of patients, whereas classical histopathological parameters such as tumour size, histological grade, and PgR were of independent prognostic significance.

Metallothionein in human gastrointestinal cancer

Although in the gastric cancer patients no association was found between the MT concentration and the clinicopathological parameters, the strong MT expression in areas with intestinal metaplasia, known to have neoplastic potential, points to a relationship between this antioxidant metalloprotein and the malignant character of cells.

Immunohistochemical study of metallothionein in pancreatic carcinomas

The expression of metallothioneins in pancreatic tumors was related to metastasis, poor prognosis and poor histological grading and the in vitro study of tumor sensitivity to cisplatin showed no significant correlation between met allothionein expression and resistance to cis Platin.

Immunohistochemical metallothionein expression in colorectal adenocarcinoma: correlation with tumour stage and patient survival

It is concluded that immunohistochemically demonstrated MT expression is significantly associated with tumour stages but does not represent an independent prognostic variable in colorectal cancer, however, it may provide important information about some of the biological mechanisms underlying progression in colors.
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