FAP-1 (Fas-associated phosphatase-1) protects pancreatic carcinoma cells from fas induced apoptosis

Background: Previously we have demonstrated that, despite normal expression of Fas (CD95, APO-1), the majority of pancreatic adenocarcinoma cell lines was resistant to the apoptosis-inducing function of this death receptor. T his observation could be explained by expression of an inhibitory protein t hat blocks Fas signal transduction. Methods: Since resistance of pancreatic carcinoma cells correlated with exp ression of the protein tyrosine phosphatase FAP-1, we investigated the func tional role of FAP-1 as a potential inhibitor of Fas-mediated apoptosis. Results: Inhibition of the Fas/FAP-1 interaction in the Fas-resistant, FAP- l-positive cell line Panc89 by cytoplasmic microinjection of a synthetic tr ipeptide (Ac-Ser-Leu-Val) mimicking the C-terminus of Fas resulted in a I-f old increase in apoptosis (after Fas stimulation) compared to cells that re ceived a negative control peptide (Ac-Ser-Leu-Tyr). Furthermore, stable tra nsfection of the Fas-sensitive, FAP-l-negative cell line Capan1 with a FAP- 1 cDNA strongly decreased sensitivity to Fas-induced apoptosis. Conclusion: These results show that FAP-1 can protect pancreatic carcinoma cells from Fas-mediated apoptosis thereby extending previous findings in T- cells to cells not belonging to the immune system.