Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis

Faller, William J.; Rafferty, Máirín; Hegarty, Shauna; Gremel, Gabriela; Ryan, Denise; Fraga, Mario F.; Esteller, Manel; Dervan, P.; Gallagher, William M.

doi:10.1097/cmr.0b013e32833d32a6

Cited by 47 publications

(29 citation statements)

References 29 publications

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“…Regarding MT isoforms, MT-1E and MT-1G were also downregulated in lung cancer tissues (Table 2), consistent with their methylation status and reduced expression in malignancies [12-14]. …”

Section: Resultssupporting

confidence: 62%

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Liang

et al. 2013

World J Surg Onc

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BackgroundNuclear factor (erythroid-derived 2)-like (Nrf)2 and metallothionein have been implicated in carcinogenesis. This study investigated the expression of Nrf2 and of Nrf2-targeted genes (NQO1 and GCLC) and the genes for the metallothionein (MT) isoforms (MT-1A and MT-2A) in human lung cancer and cancer-surrounding tissues.MethodsSurgically removed lung cancer samples (n = 80) and cancer-surrounding tissues (n = 38) were collected from Zunyi Medical College Hospital, China. Total RNA was extracted, purified, and used for real-time reverse transcription-PCR analysis of interested genes.ResultsExpression of the Nrf2-targed genes NQO1 and GCLC tended to be higher (30 to 60%) in lung cancers, but was not significantly different from that in peri-cancer tissues. By contrast, expression of the genes for M)-1A, MT-2A, and the metal transcription factor MTF-1 were three-fold to four-fold lower in lung cancers.ConclusionIn surgical samples of lung cancer, MT expression was generally downregulated, whereas Nrf2 expression tended to be upregulated. These changes could play an integral role in lung carcinogenesis.

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“…Regarding MT isoforms, MT-1E and MT-1G were also downregulated in lung cancer tissues (Table 2), consistent with their methylation status and reduced expression in malignancies [12-14]. …”

Section: Resultssupporting

confidence: 62%

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Liang

et al. 2013

World J Surg Onc

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“…MMPs play a crucial role in proliferation, invasion, metastasis and apoptosis of tumor cells (15)(16)(17). Faller WJ founded that MMPs have a significant effect on tumor resistance to gemcitabine (29). These research results were consistent with our data.…”

Section: Discussionsupporting

confidence: 91%

Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV

Cui

Wang

et al. 2018

Oncol Lett

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Chemotherapy is an important comprehensive treatment for breast cancer, which targets micro-environment of tumors as well as their characterisitcs. A previous microarray analysis revealed that matrix metalloproteinase (MMP)-1 was highly upregulated in carcinoma-associated fibroblasts (CAFs) prior to and following treatment with Taxotere under co-culture conditions. However, whether the chemotherapeutic effects of Taxotere were influenced by the changes in MMP-1 remained unclear. The purpose of the present study was to investigate the impact and mechanism of CAFs in regulating the efficacy of Taxotere on breast cancer cells. CAFs isolated from primary invasive ductal human breast tumors following surgical resection, were used in co-culture with MDA-MB-231 cells to simulate the tumor micro-environment. Following the addition of Taxotere, changes in MMP-1 gene and protein expression were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Proliferation, invasion and apoptosis assays revealed that when MMP-1 was upregulated in CAFs, the therapeutic efficacy of Taxotere was reduced in breast cancer cells. Chemosensitivity was significantly increased when MMP-1 expression was inhibited by GM6001. In addition, Collagen IV was upregulated in CAFs following chemotherapy and protected breast cancer cells against chemotherapeutic side effects. Collagen IV expression significantly decreased, as well as MMP-1 expression when GM6001 was added. Proliferation and invasion assays demonstrated that the exogenous addition of Collagen IV weakend the chemotherapeutic effect of Taxotere on breast tumor cells. Overall, the results revealed that in CAFs, MMP-1 synergized with Collagen IV as a key gene in regulating the chemotherapeutic effect of Taxotere on breast tumor cells and served an important role in reducing the efficacy of Taxotere on breast cancer, potentially via the transforming growth factor-β signaling pathway. These fidings provide a theoretical basis for the mechanism of CAFs in reducing the chemotherapeutic effect of Taxotere on breast cancer cells and a novel approach for enhancing the chemosensitivity of tumors.

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“…From this study, it could be concluded that MT1F is a putative tumor suppressor gene in colon carcinogenesis [105]. In another study, Faller et al [106] observed DNA methylation in MT1E in malignant melanoma, which suggests that MT1E is also a potential tumor suppressor gene.…”

Section: The Role Of Mt In Cancer and Apoptosismentioning

confidence: 72%

The Role of Metallothionein in Oxidative Stress

Ruttkay-Nedecký

Nejdl

Gumulec

et al. 2013

IJMS

683

435

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Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive. The free radicals are also known to play a dual role in biological systems, as they can be either beneficial or harmful for living systems. It is clear that there are numerous mechanisms participating on the protection of a cell against free radicals. In this review, our attention is paid to metallothioneins (MTs) as small, cysteine-rich and heavy metal-binding proteins, which participate in an array of protective stress responses. The mechanism of the reaction of metallothioneins with oxidants and electrophilic compounds is discussed. Numerous reports indicate that MT protects cells from exposure to oxidants and electrophiles, which react readily with sulfhydryl groups. Moreover, MT plays a key role in regulation of zinc levels and distribution in the intracellular space. The connections between zinc, MT and cancer are highlighted.

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Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis

Cited by 47 publications

References 29 publications

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Upregulating MMP‑1 in carcinoma‑associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV

The Role of Metallothionein in Oxidative Stress

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