Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar 15;9(6):469-76.
doi: 10.4161/cbt.9.6.10979. Epub 2010 Mar 20.

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

Yihui Shi  1 , Khalid Amin, Barbara G Sato, Steven J Samuelsson, Lidia Sambucetti, Zishan A Haroon, Keith Laderoute, Brian J Murphy
Affiliations

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

Yihui Shi et al. Cancer Biol Ther. .

Abstract

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 anti-human 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Detecion of MTF-1 protein in cultured human cells. human breast (MCF-10Ca1a, MCF-7) and lung (a549) carcinoma cells were grown to subconfluence, and whole cell extracts were used for immunoblotting. To confirm the specificity of the antibody for MTF-1 protein, MCF-7 cells were transfected with scrambled control or MTF-1 siRNa duplexes 6 d before harvesting for total protein.
Figure 2
Figure 2
MTF-1 immunofluorescence detection in a human breast cancer line. MCF-10Ca1a breast cancer cells were cultured and labeled with (A) affinity -purified MTF-1 antibody, (B) pre-immune serum, (C) immunogen-blocked MTF-1 antibody, and (D) random, control peptide-blocked MTF-1 antibody. Each panel is a merged composite of DAPI labeling (pseudo-colored blue), MTF-1 (red) and DIC (grey) in registration.
Figure 3
Figure 3
Representative IHC analysis of MTF-1 expression in normal tissue sections from a human. TMA (x200 magnification). IHC analysis of MTF-1 expression in six normal human tissues.
Figure 4
Figure 4
Representative IHC analysis of MTF-1 expression in normal and cancer tissue sections from a human. TMA (x200 magnification). IHC analysis of MTF-1 expression in normal and tumor tissues of human lung, cervix, breast, liver and testis.
Figure 5
Figure 5
MTF-1 expression is elevated in human breast cancer tumor tissue compared with normal surrounding tissue. Clinical human breast tumor specimens (71) were immunostained using the MTF-1 antibody. (A) Representative image shows both tumor and normal surrounding tissues in one field taken at x100 magnification. (B and C) Increased magnification (x400) of tumor (B) and normal tissue (C).
See this image and copyright information in PMC

References

    1. Lichtlen P, Schaffner W. Putting its fingers on stressful situations: the heavy metal-regulatory transcription factor MTF-1. Bioessays. 2001;23:1010–7. - PubMed
    1. Laity JH, Andrews GK. Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1). Arch Biochem Biophys. 2007;463:201–10. - PubMed
    1. Wang Y, Wimmer U, Lichtlen P, Inderbitzin D, Stieger B, Meier PJ, et al. Metal-responsive transcription factor-1 (MTF-1) is essential for embryonic liver development and heavy metal detoxification in the adult liver. Faseb J. 2004;18:1071–9. - PubMed
    1. Adilakshmi T, Laine RO. Ribosomal protein S25 mRNA partners with MTF-1 and La to provide a p53-mediated mechanism for survival or death. J Biol Chem. 2002;277:4147–51. - PubMed
    1. Bellingham SA, Coleman LA, Masters CL, Camakaris J, Hill AF. Regulation of prion gene expression by transcription factors SP1 and metal transcription factor-1. J Biol Chem. 2009;284:1291–301. - PubMed

Publication types

MeSH terms

LinkOut - more resources