Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive to tumor necrosis factor-related apoptosis-inducing ligand.

摘要: Fas (APO-1/CD95) is a transmembrane protein of the tumor necrosis factor (TNF)/nerve growth receptor superfamily that induces apoptosis in susceptible normal and neoplastic cells upon cross-linking by its ligand (FasL). TNF-related apoptosis-inducing (TRAIL) more recently identified member TNF has been shown to selectively kill engaging two cell-surface receptors, DR4 DR5. Two additional TRAIL receptors (DcR1 DcR2) do not transmit an apoptotic signal have proposed confer protection from TRAIL-induced apoptosis. We addressed expression Fas, DR4, DR5 thyroid carcinoma cell lines 31 specimens Western blot analysis immunohistochemistry, respectively, tested sensitivity Fas- was found be expressed most tissue specimens. Although did induce lines, Fas-mediated occur presence synthesis inhibitor cycloheximide, suggesting short-lived pathway these cells. Cross-linking failed recruitment activation caspase 8, whereas transfection constitutively active 8 construct effectively killed SW579 papillary line, arguing action putative occurs upstream 8. By contrast, recombinant induced 10 12 tested, activating caspase-10 at level triggering caspase-mediated cascade. Resistance correlate with DcR1 or DcR2 overcome inhibition 50% resistant lines. One medullary line Fas-and apoptosis, even caspase-8, different regulation pathway. Our observations indicate kills carcinomas originate follicular epithelium gland, inducing may provide potentially potent therapeutic reagent against cancer.