Down-regulation of cobalt-induced HIF-1alpha expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells.
Previously we reported that the hypoxia-inducible factor-1alpha (HIF-1alpha) expression correlated with cell proliferation and apoptosis under 500 mM of CoCl2 treatment in a human gastric carcinoma cell line, MKN-1. Herein we report a similar correlation in other cell lines, MKN-45 and TMK-1. The dual-phase expression of HIF-1alpha was highest at 6 and 8 h of treatment in MKN-45 and TMK-1, respectively, while the peak in MKN-1 occurred at 4 h. The cell viability indices showed a similar dual phase to the HIF-1alpha expression, while the apoptotic indices started to increase as the level of the HIF-1alpha expression decreased. In our previous study, the FACS analysis showed a marked G2/M arrest and an increase of the pre-G1 area in MKN-1 after 36 h of treatment, whereas the G2/M arrest was not observed in MKN-45 and TMK-1. The expression of cell cycle and apoptosis-related proteins showed a correlation with the HIF-1alpha expression and the FACS results, which suggested that the level of HIF-1alpha correlated with proliferation and apoptosis in human gastric carcinoma cell lines with a possible cell-type specific pattern.
Ardyanto
Tonang Dwi
TD
Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Tottori 683-8503, Japan.
Osaki
Mitsuhiko
M
Nagahama
Yumi
Y
Yamaga
Kensaku
K
Maeta
Noritaka
N
Tamura
Takayuki
T
Ito
Hisao
H
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003035:Cobalt / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007150:Immunohistochemistry; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; C018021:cobaltous chloride