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Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway.

Publication ,  Journal Article
Ni, J; Wen, X; Yao, J; Chang, H-C; Yin, Y; Zhang, M; Xie, S; Chen, M; Simons, B; Chang, P; di Sant'Agnese, A; Messing, EM; Yeh, S
Published in: Cancer Res
November 1, 2005

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.

Duke Scholars

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

November 1, 2005

Volume

65

Issue

21

Start / End Page

9807 / 9816

Location

United States

Related Subject Headings

  • Vitamin E
  • Transplantation, Heterologous
  • Trans-Activators
  • Proto-Oncogene Proteins c-akt
  • Prostatic Neoplasms
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
 

Citation

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Ni, J., Wen, X., Yao, J., Chang, H.-C., Yin, Y., Zhang, M., … Yeh, S. (2005). Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res, 65(21), 9807–9816. https://doi.org/10.1158/0008-5472.CAN-05-1334
Ni, Jing, Xingqiao Wen, Jorge Yao, Hong-Chiang Chang, Yi Yin, Min Zhang, Shaozhen Xie, et al. “Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway.Cancer Res 65, no. 21 (November 1, 2005): 9807–16. https://doi.org/10.1158/0008-5472.CAN-05-1334.
Ni J, Wen X, Yao J, Chang H-C, Yin Y, Zhang M, et al. Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res. 2005 Nov 1;65(21):9807–16.
Ni, Jing, et al. “Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway.Cancer Res, vol. 65, no. 21, Nov. 2005, pp. 9807–16. Pubmed, doi:10.1158/0008-5472.CAN-05-1334.
Ni J, Wen X, Yao J, Chang H-C, Yin Y, Zhang M, Xie S, Chen M, Simons B, Chang P, di Sant’Agnese A, Messing EM, Yeh S. Tocopherol-associated protein suppresses prostate cancer cell growth by inhibition of the phosphoinositide 3-kinase pathway. Cancer Res. 2005 Nov 1;65(21):9807–9816.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

November 1, 2005

Volume

65

Issue

21

Start / End Page

9807 / 9816

Location

United States

Related Subject Headings

  • Vitamin E
  • Transplantation, Heterologous
  • Trans-Activators
  • Proto-Oncogene Proteins c-akt
  • Prostatic Neoplasms
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude