The Role of Metallothioneins in Carcinogenesis

Dzięgiel, Piotr; Puła, Bartosz; Kobierzycki, Christopher; Stasiołek, Mariusz; Podhorska-Okołów, Marzena

doi:10.1007/978-3-319-27472-0_4

Cited by 7 publications

(8 citation statements)

References 241 publications

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“…Theocharis et al also observed that among lung cancer subtypes, MT expression was prominent in squamous cell lung carcinoma and adenocarcinoma but absent in small cell lung cancer [ 27 ]. The differential expression of MTs depends on the type and differentiation status of tumors, as well as other environmental stimuli and/or gene mutations [ 17 , 28 , 29 ]. Nevertheless, a better understanding of the changes in the expression of particular MT isoforms in various cancers can help identify specific therapeutic targets and reverse tumor progression.…”

Section: Introductionmentioning

confidence: 99%

The roles of metallothioneins in carcinogenesis

2018

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Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in metal homeostasis and protection against heavy metal toxicity, DNA damage, and oxidative stress. In humans, MTs have four main isoforms (MT1, MT2, MT3, and MT4) that are encoded by genes located on chromosome 16q13. MT1 comprises eight known functional (sub)isoforms (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X). Emerging evidence shows that MTs play a pivotal role in tumor formation, progression, and drug resistance. However, the expression of MTs is not universal in all human tumors and may depend on the type and differentiation status of tumors, as well as other environmental stimuli or gene mutations. More importantly, the differential expression of particular MT isoforms can be utilized for tumor diagnosis and therapy. This review summarizes the recent knowledge on the functions and mechanisms of MTs in carcinogenesis and describes the differential expression and regulation of MT isoforms in various malignant tumors. The roles of MTs in tumor growth, differentiation, angiogenesis, metastasis, microenvironment remodeling, immune escape, and drug resistance are also discussed. Finally, this review highlights the potential of MTs as biomarkers for cancer diagnosis and prognosis and introduces some current applications of targeting MT isoforms in cancer therapy. The knowledge on the MTs may provide new insights for treating cancer and bring hope for the elimination of cancer.

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Section: Introductionmentioning

confidence: 99%

The roles of metallothioneins in carcinogenesis

2018

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“…Our results support the latter finding. The potential mechanism underlying the differences in mRNA expression of MT isoforms between the analyzed lesions have not yet been determined, however, the redox potential of thyroid cells during malignant transformation may impact the level of MT expression due to the redox sensitive nature of regulatory mechanism (14,20). The observed strong positive correlations between mRNA expression of particular MT isoforms seem to support this hypothesis.…”

Section: Discussionmentioning

confidence: 76%

“…Due to their high cysteine content, MTs are involved in numerous cell processes such as binding and transport of zinc and copper ions, detoxification of heavy metals, scavenging of free radicals, and cell differentiation, proliferation and apoptosis (14,20,21). Furthermore, MT1, MT2 and MT3 may protect cells from certain chemotherapeutic agents or radiation-induced damage (22,23).…”

Section: Mt1c Mt1d Mt1i Mt1j Mt1k Mt1lmentioning

confidence: 99%

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Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions

Wojtczak

Puła

Gomułkiewicz

et al. 2017

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“…It has been demonstrated that increased expression of MT-1 and MT-2 is associated with greater proliferative potential of tumor cells and is correlated with a more rapid course of the disease and poorer prognosis (17)(18)(19)(20)(21)(22)(23)(24). It has also been shown that MT-1 and MT-2 are involved in the development of cancer cell resistance to chemotherapy and radiotherapy (25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Expression of metallothionein 3 in ductal breast cancer

Gomułkiewicz

Jabłońska

Puła

et al. 2016

International Journal of Oncology

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Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.

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The Role of Metallothioneins in Carcinogenesis

Cited by 7 publications

References 241 publications

The roles of metallothioneins in carcinogenesis

The roles of metallothioneins in carcinogenesis

Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions

Expression of metallothionein 3 in ductal breast cancer

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