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
. 2015 Apr;135(4):1147-1156.
doi: 10.1038/jid.2014.514. Epub 2014 Dec 10.

Arsenite-mediated promotion of anchorage-independent growth of HaCaT cells through placental growth factor

Ichiro Yajima  1 , Mayuko Y Kumasaka  1 , Shoko Ohnuma  2 , Nobutaka Ohgami  1 , Hisao Naito  3 , Hossain U Shekhar  4 , Yasuhiro Omata  3 , Masashi Kato  5
Affiliations
Free article

Arsenite-mediated promotion of anchorage-independent growth of HaCaT cells through placental growth factor

Ichiro Yajima et al. J Invest Dermatol. 2015 Apr.
Free article

Abstract

Various cancers including skin cancer are increasing in 45 million people exposed to arsenic above the World Health Organization's guideline value of 10 μg l(-1). However, there is limited information on key molecules regulating arsenic-mediated carcinogenesis. Our fieldwork in Bangladesh demonstrated that levels of placental growth factor (PlGF) in urine samples from residents of cancer-prone areas with arsenic-polluted drinking water were higher than those in urine samples from residents of an area that was not polluted with arsenic. Our experimental study in human nontumorigenic HaCaT skin keratinocytes showed that arsenite promoted anchorage-independent growth with increased expression and secretion of PlGF, a ligand of vascular endothelial growth factor receptor1 (VEGFR1), and increased VEGFR1/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) activities. The arsenite-mediated promotion of anchorage-independent growth was strongly inhibited by PlGF depletion with decreased activities of the PlGF/VEGFR1/MEK/ERK pathway. Moreover, arsenite proteasome-dependently degrades metal-regulatory transcription factor-1 (MTF-1) protein, resulting in a decreased amount of MTF-1 protein binding to the PlGF promoter. MTF-1 negatively controlled PlGF transcription in HaCaT cells, resulting in increased PlGF transcription. These results suggest that arsenite-mediated MTF-1 degradation enhances the activity of PlGF/VEGFR1/MEK/ERK signaling, resulting in promotion of the malignant transformation of keratinocytes. Thus, this study proposed a molecular mechanism for arsenite-mediated development of skin cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nat Rev Cancer. 2008 Dec;8(12 ):942-56 - PubMed
    1. Water Sci Technol. 2002;46(11-12):375-80 - PubMed
    1. Cell. 2007 Nov 2;131(3):463-75 - PubMed
    1. Crit Rev Toxicol. 1995;25(5):397-462 - PubMed
    1. IARC Monogr Eval Carcinog Risks Hum. 2004;84:1-477 - PubMed

Publication types

MeSH terms

LinkOut - more resources

-