| RRC ID |
45406
|
| Author |
Yajima I, Kumasaka MY, Ohnuma S, Ohgami N, Naito H, Shekhar HU, Omata Y, Kato M.
|
| Title |
Arsenite-mediated promotion of anchorage-independent growth of HaCaT cells through placental growth factor.
|
| Journal |
J Invest Dermatol
|
| 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.
|
| Volume |
135(4)
|
| Pages |
1147-1156
|
| Published |
2015-4-1
|
| DOI |
10.1038/jid.2014.514
|
| PII |
S0022-202X(15)37216-X
|
| PMID |
25493652
|
| MeSH |
Animals
Arsenic / chemistry
Arsenic / toxicity*
Arsenic Poisoning / metabolism*
Arsenites / chemistry*
Arsenites / urine
Bangladesh
Cell Adhesion
Cell Line
Cell Line, Tumor
Cell Transformation, Neoplastic
Disease Models, Animal
Environmental Pollutants
Humans
Immunohistochemistry
Keratinocytes / drug effects
MAP Kinase Kinase Kinases / metabolism
Mice
Placenta Growth Factor
Pregnancy Proteins / metabolism
Pregnancy Proteins / physiology*
Pregnancy Proteins / urine
Proteasome Endopeptidase Complex / chemistry
RNA Interference
RNA, Messenger / metabolism
Signal Transduction
Skin Neoplasms / chemically induced*
Urine / chemistry
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Water Pollutants, Chemical / urine
|
| IF |
7.143
|
| Times Cited |
13
|
|
WOS Category
|
DERMATOLOGY
|
| Resource |
| Human and Animal Cells |
A431 |
