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 A. Neuwelt; Barbara M. Mueller; Carol A. Kruse

doi:10.1016/j.bbrc.2009.03.126

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 A. Neuwelt
, Barbara M. Mueller
, Carol A. Kruse

Neurology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 language	English (US)
Pages (from-to)	167-171
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	383
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2009.03.126
State	Published - May 29 2009

Funding

Dr. Joan Massague supplied the 1833 breast cancer cell line. Dr. L.E. Gerschenson provided feedback to us for apoptosis assessments. Supported by NIH Grant NS056300 and the R. Herbert and Alma S. Manweiler Memorial Research Fund, and the Joan S. Holmes Fellowship.

Funders	Funder number
R. Herbert and Alma S. Manweiler Memorial Research Fund
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Institute of Neurological Disorders and Stroke	R21NS056300

Keywords

Apoptosis
Astrocytomas
Breast Cancer
Fas
FasL
Ribozyme
siRNA

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2009.03.126

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title = "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.",

keywords = "Apoptosis, Astrocytomas, Breast Cancer, Fas, FasL, Ribozyme, siRNA",

author = "Richard Tritz and Hickey, \{Michelle J.\} and Lin, \{Amy H.\} and Philipp Hadwiger and Sah, \{Dinah W.Y.\} and Neuwelt, \{Edward A.\} and Mueller, \{Barbara M.\} and Kruse, \{Carol A.\}",

note = "Funding Information: Dr. Joan Massague supplied the 1833 breast cancer cell line. Dr. L.E. Gerschenson provided feedback to us for apoptosis assessments. Supported by NIH Grant NS056300 and the R. Herbert and Alma S. Manweiler Memorial Research Fund, and the Joan S. Holmes Fellowship.",

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AU - Tritz, Richard

AU - Hickey, Michelle J.

AU - Lin, Amy H.

AU - Hadwiger, Philipp

AU - Sah, Dinah W.Y.

AU - Neuwelt, Edward A.

AU - Mueller, Barbara M.

AU - Kruse, Carol A.

N1 - Funding Information: Dr. Joan Massague supplied the 1833 breast cancer cell line. Dr. L.E. Gerschenson provided feedback to us for apoptosis assessments. Supported by NIH Grant NS056300 and the R. Herbert and Alma S. Manweiler Memorial Research Fund, and the Joan S. Holmes Fellowship.

PY - 2009/5/29

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N2 - 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.

AB - 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.

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KW - FasL

KW - Ribozyme

KW - siRNA

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

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