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

Richard Tritz, Michelle J. Hickey, Amy H. Lin, Philipp Hadwiger, Dinah W Y Sah, Edward Neuwelt, Barbara M. Mueller, Carol A. Kruse

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume383
Issue number2
DOIs
StatePublished - May 29 2009

Fingerprint

Small Interfering RNA
Tumors
Down-Regulation
Genes
Cells
Apoptosis
Neoplasms
Transport Vesicles
Catalytic RNA
Gene Targeting
Cell membranes
Transferases
Gene expression
Glioma
Transfection
Colon
Cell Count
Cell Membrane
Breast Neoplasms
Carcinoma

Keywords

  • Apoptosis
  • Astrocytomas
  • Breast Cancer
  • Fas
  • FasL
  • Ribozyme
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

FAPP2 gene downregulation increases tumor cell sensitivity to Fas-induced apoptosis. / Tritz, Richard; Hickey, Michelle J.; Lin, Amy H.; Hadwiger, Philipp; Sah, Dinah W Y; Neuwelt, Edward; Mueller, Barbara M.; Kruse, Carol A.

In: Biochemical and Biophysical Research Communications, Vol. 383, No. 2, 29.05.2009, p. 167-171.

Research output: Contribution to journalArticle

Tritz, Richard ; Hickey, Michelle J. ; Lin, Amy H. ; Hadwiger, Philipp ; Sah, Dinah W Y ; Neuwelt, Edward ; Mueller, Barbara M. ; Kruse, Carol A. / FAPP2 gene downregulation increases tumor cell sensitivity to Fas-induced apoptosis. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 383, No. 2. pp. 167-171.
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