FAPP2 gene downregulation increases tumor cell sensitivity to Fas-induced apoptosis.

Abstract

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 trans-Golgi to the plasma membrane. The introduction of ribozymes targeting the FAPP2 gene in colon carcinoma cells induced their apoptosis in the presence of Fas agonistic antibody. Furthermore, by quantitative PCR we showed that a siRNA specific to FAPP2, but not a randomized siRNA control, reduced FAPP2 gene expression in tumor cells. Transfection of FAPP2 siRNA into human tumor cells then incubated with FasL resulted in reduction of viable cell numbers. Also, FAPP2 siRNA transfected glioma and breast tumor cells showed significant increases in apoptosis upon incubation with soluble FasL, but the apoptosis did not necessarily correlate with increased Fas expression. These data demonstrate a previously unknown role for FAPP2 in conferring resistance to apoptosis and indicate that FAPP2 may be a target for cancer therapy.

• Authors: Richard Tritz, Michelle J Hickey, Amy H Lin, Philipp Hadwiger, Dinah W Y Sah, Edward A Neuwelt, Barbara M Mueller, Carol A Kruse
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 383 Issue 2 Pg. 167-71 (May 29 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19341712 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies
• Fas Ligand Protein
• PLEKHA8 protein, human
• RNA, Small Interfering

Topics

• Adaptor Proteins, Signal Transducing (genetics, physiology)
• Antibodies (immunology)
• Apoptosis (genetics)
• Cell Line, Tumor
• Down-Regulation
• Fas Ligand Protein (agonists, immunology, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasms (metabolism, pathology)
• RNA, Small Interfering (genetics)