A FAS receptor szerepe a colon carcinoma sejtek DNS-károsodás okozta sejthalálában

Translated title of the contribution: Role of FAS receptor in the DNA damage induced apoptosis of colon carcinoma cells

Peták István, David M. Tillman, Frank Harwood, Alice Gibson, Janet A. Houghton

Research output: Contribution to journalArticle

Abstract

Thymidineless death is the mechanism of cell killing associated with 5-fluorouracil (5-FU) in colon cancer and is the most effective therapy for this disease when combined with reduced folate Leucovorin that targets 5-FU to the thymidylate synthase (TS-) locus. Thymidylate synthase-deficient colon carcinoma cells (TS-) underwent rapid apoptosis following thymidin CdThD) deprivation. Apoptosis was induced in TS- cells concomitantly with it pregnlated FAS ligand expression, and blocked by the exposure to the NOK-1 MoAb that prevents the ligation of FAS ligand to FAS receptor. There was a close correlation between loss of clonogenic survival and the induction of thimidineless stress-induced apoptosis. This study has subsequently compared the role of the Fas signaling pathway in apoptosis induced by other modes of DNA damage following treatment with etoposide, doxorubicin and topotecan. Drug concentrations that induced 50% apoptosis (FACS analysis) at 72 hr (30pM etoposide, 1 pM doxorubicin, 1 pM topotecan) also induced similar levels of FasL expression. Hoivever, 100-fold lower drug concentrations were found to result in the loss of clonogenic potential in the absence of detectable apoptosis or FasL expression. Drug- induced loss in clonogenicity was not inhibited by treatment with NOK-1. TS- cells selected for resistance to the cytolytic anti-Fas MoAb CH-11 demonstrated cross resistance to thymineless death following dThd deprivation, but maintained sensitivity to all three DNA damaging agents. Data indicate that thymineless death is regulated via Fas and is closely linked to apoptosis, whereas other modes of DNA damages may induce loss of clonogenicity prior to the induction of apoptosis and FasL expression and are independent of the Fas signaling pathway.

Translated title of the contributionRole of FAS receptor in the DNA damage induced apoptosis of colon carcinoma cells
Original languageHungarian
Pages (from-to)101-109
Number of pages9
JournalMagyar onkologia
Volume43
Issue number2
Publication statusPublished - Dec 1 1999

ASJC Scopus subject areas

  • Medicine(all)

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    István, P., Tillman, D. M., Harwood, F., Gibson, A., & Houghton, J. A. (1999). A FAS receptor szerepe a colon carcinoma sejtek DNS-károsodás okozta sejthalálában. Magyar onkologia, 43(2), 101-109.