Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma.
Cells undergoing apoptosis are characterized by decreased cell size due to changes in intracellular ion concentration and rapid, aquaporin (AQP)-dependent water movement out of the cell, events required for the activation of pro-apoptotic enzymes. The current study demonstrates AQP 8 and 9 expression is significantly decreased in hepatocellular carcinoma (HCC) versus normal liver. Isolation of hepatic tumor cells (H4IIE) and hepatocytes confirmed a lack of water movement across the H4IIE cell membrane via AQPs and identified an inherent resistance of H4IIE cells to apoptotic stimuli. In contrast, hepatocytes rapidly responded to osmotic challenge through AQP-dependent water movement and underwent cell death following apoptotic stimulation.
Jablonski
Elizabeth M
EM
Department of Biology, UNC at Charlotte, 9201 University City Blvd., Charlotte, NC, USA.
Mattocks
M Adrian
MA
Sokolov
Eugene
E
Koniaris
Leonidas G
LG
Hughes
Francis M
FM
Fausto
Nelson
N
Pierce
Robert H
RH
McKillop
Iain H
IH
D000818:Animals; D017209:Apoptosis; D020346:Aquaporins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011912:Rats, Inbred ACI; D014867:Water / Q000378:metabolism
C491638:Aqp9 protein, mouse; D020346:Aquaporins; C108330:aquaporin 8; D014867:Water