Highly increased TNF sensitivity of tumor cells expressing the yeast delta 9-desaturase gene.
L929 and WEHI tumor cell lines were genetically modified to constitutively express the Saccharomyces cerevisiae Ole 1 gene, coding for the delta 9-desaturase enzyme. These cells exhibit an increased ratio of monounsaturated fatty acids in their membrane phospholipids paralleled by an overall decrease in the membrane molecular order and a highly increased tumor necrosis factor-alpha (TNF) sensitivity. The TNF-alpha signaling cascade involves events, like receptor clustering and cleavage of membrane constituent lipid molecules by phospholipases, which are influenced by the physical state of cellular membranes. We discuss the possible involvement of non-bilayer forming lipids in the control of signaling mechanisms leading to TNF cytotoxicity.
Györfy
Z
Z
Institute of Biochemistry, Biol. Research Center, Szeged, Hungary.
Benkö
S
S
Kusz
E
E
Maresca
B
B
Vígh
L
L
Duda
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D012513:Sarcoma, Experimental / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase