RRC ID 38522
著者 Thang ND, Yajima I, Kumasaka MY, Ohnuma S, Yanagishita T, Hayashi R, Shekhar HU, Watanabe D, Kato M.
タイトル Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase.
ジャーナル PLoS One
Abstract Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.
巻・号 6(10)
ページ e25636
公開日 2011-1-1
DOI 10.1371/journal.pone.0025636
PII PONE-D-11-06873
PMID 22022425
PMC PMC3192110
MeSH Animals Arsenic / analysis Arsenic / toxicity Bangladesh Barium / analysis Barium / toxicity* CSK Tyrosine-Protein Kinase Cell Adhesion / drug effects Cell Movement / drug effects* Cell Proliferation / drug effects Cell Transformation, Neoplastic / pathology Enzyme Activation / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism Fibroblasts / drug effects Fibroblasts / enzymology Fibroblasts / pathology Focal Adhesion Protein-Tyrosine Kinases / metabolism Humans Keratinocytes / drug effects Keratinocytes / enzymology* Keratinocytes / pathology* Matrix Metalloproteinase 14 / metabolism Melanocytes / drug effects Melanocytes / enzymology Melanocytes / pathology Mice NIH 3T3 Cells Protein Kinase Inhibitors / pharmacology Protein-Tyrosine Kinases / antagonists & inhibitors Protein-Tyrosine Kinases / metabolism* Vietnam Water Pollution / analysis Water Wells / chemistry src-Family Kinases
IF 2.74
引用数 17
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞 A431 NIH3T3