Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway.
Abstract
Epidemiologic studies suggested that vitamin E has a protective effect against prostate
cancer. We showed here that tocopherol-associated protein (TAP), a vitamin E-binding
protein, promoted vitamin E uptake and facilitated vitamin E antiproliferation effect
in prostate cancer cells. Interestingly, without vitamin E treatment, overexpression
of TAP in prostate cancer cells significantly suppressed cell growth; knockdown of
endogenous TAP by TAP small interfering RNA (siRNA) in nonmalignant prostate HPr-1
cells increased cell growth. Further mechanism dissection studies suggested that the
tumor suppressor function of TAP was via down-regulation of phosphoinositide 3-kinase
(PI3K)/Akt signaling, but not by modulating cell cycle arrest or androgen receptor
signaling. Immunoprecipitation results indicated that TAP inhibited the interaction
of PI3K subunits, p110 with p85, and subsequently reduced Akt activity. Constitutively
active Akt could negate the TAP-suppressive activity on prostate cancer cell growth.
Moreover, stable transfection of TAP in LNCaP cells suppressed LNCaP tumor incidence
and growth rate in nude mice. Furthermore, TAP mRNA and protein expression levels
were significantly down-regulated in human prostate cancer tissue samples compared
with benign prostate tissues as measured by reverse transcription-PCR, in situ hybridization,
and immunohistochemistry. Together, our data suggest that TAP not only mediates vitamin
E absorption to facilitate vitamin E antiproliferation effect in prostate cancer cells,
but also functions like a tumor suppressor gene to control cancer cell viability through
a non-vitamin E manner. Therefore, TAP may represent a new prognostic marker for prostate
cancer progression.
Type
Journal articleSubject
Cell Line, TumorAnimals
Humans
Mice
Mice, Nude
Prostatic Neoplasms
Vitamin E
Lipoproteins
Carrier Proteins
Trans-Activators
Transplantation, Heterologous
Neoplasm Transplantation
Cell Growth Processes
MAP Kinase Signaling System
Gene Expression
Male
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
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https://hdl.handle.net/10161/21893Published Version (Please cite this version)
10.1158/0008-5472.can-05-1334Publication Info
Ni, Jing; Wen, Xingqiao; Yao, Jorge; Chang, Hong-Chiang; Yin, Yi; Zhang, Min; ...
Yeh, Shuyuan (2005). Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition
of the phosphoinositide 3-kinase pathway. Cancer research, 65(21). pp. 9807-9816. 10.1158/0008-5472.can-05-1334. Retrieved from https://hdl.handle.net/10161/21893.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ming Chen
Associate Professor in Pathology
Our laboratory is interested in understanding the molecular and genetic events underlying
cancer progression and metastasis. The focus of our work is a series of genetically
engineered mouse models that faithfully recapitulate human disease. Using a combination
of mouse genetics, omics technologies, cross-species analyses and in vitro approaches,
we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving
metastatic cancer progression, with a long

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