Metallothionein expression in human neoplasia

  title={Metallothionein expression in human neoplasia},
  author={Stamos Theocharis and Alexandra P. Margeli and Jerzy Klijanienko and Gregorios Kouraklis},
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… 

Metallothioneins and cancer.

The role of MTs as a tumor disease marker or as a cause of resistance in cancer treatment is reviewed and discussed, and some analytical methods that were developed to detect MTs are described.

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.

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.

Differential expression of metallothioneins (MTs) 1, 2, and 3 in response to zinc treatment in human prostate normal and malignant cells and tissues

Evidence is provided of the association of attenuated MT1/2 with prostate tumor progression, and the zinc induction of MT1-2 expression resulting in cellular zinc restoration, which suggest the potential of MT 1/2 as a candidate biomarker for prostate cancer and the utilization of zinc in prostate cancer prevention and treatment.



Metallothionein: a multifunctional protein from toxicity to cancer.

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

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.


  • 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.

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.

Significance of metallothionein expression in breast myoepithelial cells

The proposition that loss of myoepithelial cells in invasive mammary cancers may be compensated in part by changes in the tumor cells is supported, which may subsequently be the basis for studying the role of MT in breast physiology and carcinogenesis.

Immunohistochemical localization of metallothionein in endometrial lesions

The data suggest that MT expression seems to be under hormonal control in normal endometrium; that it may modify p53 expression; and that it could be used as an additional biological marker indicating aggressive behaviour in endometrial lesions.

Immunohistochemical metallothionein expression in thymoma: correlation with histological types and cellular origin

Results suggest that both spindle cell thymoma and squamoid thymomas might derive from the medullary compartment of the thymus, and MT expression does not correlate with the invasive potential of different histological types of thymomes.