The metal-responsive transcription factor-1 protein is elevated in human tumors

Shi, Yihui; Amin, Khalid; Sato, Barbara; Samuelsson, Steven J.; Sambucetti, Lidia; Haroon, Zishan A.; Laderoute, Keith R.; Murphy, Brian J.

doi:10.4161/cbt.9.6.10979

Cited by 28 publications

(21 citation statements)

References 52 publications

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“…The decreased concentration of MTs then causes DNA lesions and decreases the direct reduction of Cr 6+ to Cr 3+ that is not carcinogenic (Kimura, 2010). Moreover, it was found that MTF-1 is elevated in human breast, lung, and cervical carcinoma-derived cell lines (Shi et al, 2010). This finding supports the importance of MTs in carcinogenesis.…”

Section: Mts As a Binder Of Metal Ions Involved In Carcenogenesismentioning

confidence: 66%

Metallothioneins and zinc in cancer diagnosis and therapy

Křížková¹,

Ryvolová²,

Hraběta³

et al. 2012

Drug Metabolism Reviews

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Metallothioneins (MTs) are involved in protection against oxidative stress (OS) and toxic metals and they participate in zinc metabolism and its homeostasis. Disturbing of zinc homeostasis can lead to formation of reactive oxygen species, which can result in OS causing alterations in immunity, aging, and civilization diseases, but also in cancer development. It is not surprising that altered zinc metabolism and expression of MTs are of great interest in the case of studying of oncogenesis and cancer prognosis. The role of MTs and zinc in cancer development is tightly connected, and the structure and function of MTs are strongly dependent on Zn²⁺ redox state and its binding to proteins. Antiapoptic effects of MTs and their interactions with proteins nuclear factor kappa B, protein kinase C, esophageal cancer-related gene, and p53 as well as the role of MTs in their proliferation, immunomodulation, enzyme activation, and interaction with nitric oxide are reviewed. Utilization of MTs in cancer diagnosis and therapy is summarized and their importance for chemoresistance is also mentioned.

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Section: Mts As a Binder Of Metal Ions Involved In Carcenogenesismentioning

confidence: 66%

Metallothioneins and zinc in cancer diagnosis and therapy

Křížková¹,

Ryvolová²,

Hraběta³

et al. 2012

Drug Metabolism Reviews

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“…2 After evaluating each case, 2 tumor blocks from each case were selected, and tissue microarrays (TMAs) were prepared. 14 TMA sections were stained immunohistochemically by antibodies to Glut-1, iNOS, COX-1, COX-2, and NF-jB using standard protocols established using the avidin-biotin complex staining procedure ( Fig. 1A-E).…”

Section: Methodsmentioning

confidence: 99%

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P ¼.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P ¼.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P ¼.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011;117:301-9.

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“…Notably, using xenograft implantation of wild type or MTF-1-KO simian virus 40 large T antigen immortalized, and Harvey-ras-transformed mouse embryonic fibroblasts, it has been shown that the loss of MTF-1 suppresses tumour growth (Haroon et al 2004). MTF-1 protein levels are elevated in diverse human tumour types, including breast, lung, cervical, and kidney carcinomas (Shi et al 2010). Taken together, these observations suggest that MTF-1 plays a general role in the cellular stress response and support the concept that MTF-1 is an important multi-stress sensor.…”

Section: Introductionmentioning

confidence: 99%

The phosphoinositide 3-kinase pathway and glycogen synthase kinase-3 positively regulate the activity of metal-responsive transcription factor-1 in response to zinc ions

Andéol¹,

Bonneau

Gagné

et al. 2018

Biochem. Cell Biol.

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Metal-responsive transcription factor-1 (MTF-1) is a metal-regulatory transcription factor essential for induction of the genes encoding metallothioneins (MTs) in response to transition metal ions. Activation of MTF-1 is dependent on the interaction of zinc with the zinc fingers of the protein. In addition, phosphorylation is essential for MTF-1 transactivation. We previously showed that inhibition of phosphoinositide 3-kinase (PI3K) abrogated Mt expression and metal-induced MTF-1 activation in human hepatocellular carcinoma (HCC) HepG2 and mouse L cells, thus showing that the PI3K signaling pathway positively regulates MTF-1 activity and Mt gene expression. However, it has also been reported that inhibition of PI3K has no significant effects on Mt expression in immortalized epithelial cells and increases Mt expression in HCC cells. To further characterize the role of the PI3K pathway on the activity of MTF-1, transfection experiments were performed in HEK293 and HepG2 cells in presence of glycogen synthase kinase-3 (GSK-3), mTOR-C1, and mTOR-C2 inhibitors, as well as of siRNAs targeting Phosphatase and TENsin homolog (PTEN). We showed that inhibition of the mTOR-C2 complex inhibits the activity of MTF-1 in HepG2 and HEK293 cells, while inhibition of the mTOR-C1 complex or of PTEN stimulates MTF-1 activity in HEK293 cells. These results confirm that the PI3K pathway positively regulates MTF-1 activity. Finally, we showed that GSK-3 is required for MTF-1 activation in response to zinc ions.

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The metal-responsive transcription factor-1 protein is elevated in human tumors

Cited by 28 publications

References 52 publications

Metallothioneins and zinc in cancer diagnosis and therapy

Metallothioneins and zinc in cancer diagnosis and therapy

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

The phosphoinositide 3-kinase pathway and glycogen synthase kinase-3 positively regulate the activity of metal-responsive transcription factor-1 in response to zinc ions

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