Role of metal‐responsive transcription factor‐1 (MTF‐1) in EGF‐dependent DNA synthesis in primary hepatocytes

Kimura, Toshikiro; Itoh, Norio; Sone, Tomomichi; Kondoh, Masuo; Tanaka, Keiichi; Isobe, Masakazu

doi:10.1002/jcb.20948

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…An siRNA sequence against human MTF-1 was designed from a published mouse sequence 55. The corresponding human sequence is 3'-CTG ATT CCC ATT GAA GCA CTA-5'.…”

Section: Methodsmentioning

confidence: 99%

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

Shi¹,

Amin²,

Sato³

et al. 2010

Cancer Biology & Therapy

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We previously identified metal-responsive transcription factor-1 (MTF-1) as a positive contributor to mouse fibrosarcoma growth through effects on cell survival, proliferation, tumor angiogenesis and extracellular matrix remodeling. In the present study, we investigated MTF-1 protein expression in human tissues by specific immunostaining of both normal and tumor tissue samples. Immunohistochemical (IHC) staining of a human tissue microarray (TMA), using a unique antihuman MTF-1 antibody, indicated constitutive MTF-1 expression in most normal tissues, with liver and testis displaying comparatively high levels of expression. Nevertheless, MTF-1 protein levels were found to be significantly elevated in diverse human tumor types, including breast, lung and cervical carcinomas. IHC analysis of a separate panel of full-size tissue sections of human breast cancers, including tumor and normal adjacent, surrounding tissue, confirmed and extended the results of the TMA analysis. Taken with our previous findings, this new study suggests a role for MTF-1 in human tumor development, growth or spread. Moreover, the study suggests that MTF-1 could be a novel therapeutic target that offers the opportunity to manipulate metal or redox homeostasis in tumor cells.

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“…An siRNA sequence against human MTF-1 was designed from a published mouse sequence 55. The corresponding human sequence is 3'-CTG ATT CCC ATT GAA GCA CTA-5'.…”

Section: Methodsmentioning

confidence: 99%

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

Shi¹,

Amin²,

Sato³

et al. 2010

Cancer Biology & Therapy

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“…Additionally, MTF-1 may be activated through phosphorylation induced by metal induced activation of pathways important to cell growth such as PKC, PI3K, or c-Jun N terminal Kinase (JNK) [69]. Moreover, MTF-1 has been shown to be critical for the DNA synthesis induced by epidermal growth factor (EGF) [70], which has a profound role in breast cancer [71,72]. …”

Section: The Association Of Cellular Zinc Status With Cancer Develmentioning

confidence: 99%

Zinc and Cancer: Implications for LIV-1 in Breast Cancer

2012

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Zinc is a trace mineral which is vital for the functioning of numerous cellular processes, is critical for growth, and may play an important role in cancer etiology and outcome. The intracellular levels of this mineral are regulated through the coordinated expression of zinc transporters, which modulate both zinc influx as well as efflux. LIV-1 (ZIP6) was first described in 1988 as an estrogen regulated gene with later work suggesting a role for this transporter in cancer growth and metastasis. Despite evidence of its potential utility as a target gene for cancer prognosis and treatment, LIV-1 has received relatively little attention, with only three prior reviews being published on this topic. Herein, the physiological effects of zinc are reviewed in light of this mineral’s role in cancer growth with specific attention being given to LIV-1 and the potential importance of this transporter to breast cancer etiology.

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“…We reported that inhibition of MTF-1 by dominant-negative MTF-1 88) and MTF-1 siRNA decreased epidermal growth factordependent ERK phosphorylation in primary hepatocytes. 89) Phosphorylation of ERK has been shown to be essential for cell proliferation. MTF-1 mediates MT production, and MT might modulate MTF-1 activity.…”

Section: Physiological Role Of Mt and Its Putative Mechanismmentioning

confidence: 99%

Function of Metallothionein in Gene Expression and Signal Transduction: Newly Found Protective Role of Metallothionein

Kimura

Itoh

2008

JOURNAL OF HEALTH SCIENCE

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A heavy-metal-binding protein, metallothionein (MT), is induced by heavy metal overload and reactive oxygen species (ROS). The metals and ROS are rendered harmless by binding to MT or by oxidizing MT, respectively. This is a well-known role of MT. MT is also induced by glucocorticoids and cytokines. Induced MT may increase intracellular free zinc and modulate the activity of transcription factors. Changes in MT levels are thought to help in adaptation to changes in environmental conditions. MT modulates inflammatory reactions, including lipopolysaccharide (LPS)-induced expression of cytokines, nitric oxide production from macrophages in response to LPS, and resistance to LPS/D-galactosamine-induced lethality. In this review, we focus on a newly found protective role of MT, which acts mainly via changes in intracellular zinc levels or modulation of gene expression.

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Role of metal‐responsive transcription factor‐1 (MTF‐1) in EGF‐dependent DNA synthesis in primary hepatocytes

Cited by 8 publications

References 35 publications

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

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

Zinc and Cancer: Implications for LIV-1 in Breast Cancer

Function of Metallothionein in Gene Expression and Signal Transduction: Newly Found Protective Role of Metallothionein

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