Abstract #5125: FAPP2 gene downregulation in human colon, breast and glial tumor cells increases their sensitivity to Fas/FasL induced apoptosis.

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO The gene for phosphatidylinositol-4-phosphate adaptor-2 (FAPP2) encodes a cytoplasmic lipid transferase with a plekstrin homology domain that has been implicated in vesicle maturation and transport from the trans-Golgi to the plasma membrane. Initial experiments with target validation ribozymes indicated that reducing the expression of FAPP2 could sensitize colon carcinoma cells to apoptosis induced by Fas agonistic antibody. After demonstrating that tumor cells express FAPP2 mRNA, we designed a siRNA specific to FAPP2 and showed that this siRNA, but not a randomized siRNA control, reduced FAPP2 expression in tumor cells as determined by quantitative PCR. Transfection of FAPP2 siRNA into human tumor cells that were then incubated with FasL, resulted in reduction of viable cell numbers as determined by the MTT colorimetric assay. Further studies using glioma and breast tumor cells showed that significantly increased apoptosis occurred upon incubation of FAPP2 siRNA transfected cells with soluble FasL, as shown by a morphologic acridine orange/ethidium bromide apoptotic assay. These data demonstrate a previously unknown role for FAPP2 in conferring resistance to apoptosis and indicate that FAPP2 may be a potential target for the therapy of cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5125.