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Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB.

Publication ,  Journal Article
Raj, GV; Sekula, JA; Guo, R; Madden, JF; Daaka, Y
Published in: Prostate
October 1, 2004

BACKGROUND: Dysregulated cell survival contributes to the poor efficacy of many chemotherapeutic regimens for patients with advanced prostate cancer. In this study we examined ability of the lipid growth factor lysophosphatidic acid (LPA), a G protein-coupled receptor (GPCR) ligand, to promote prostate cell survival. METHODS: PC3 cells were used as a model to study mechanisms involved in survival of androgen-insensitive prostate cancer cells. Cell survival was measured by FACS analysis of cell cycle parameters after propidium iodide or annexin V and 7-AAD immunostaining. Activation state of nuclear facor-kappaB (NF-kappaB) was determined biochemically by nuclear translocation and transcriptional activation. Human tissue was analyzed for nuclear expression of NF-kappaB by immunohistochemistry. RESULTS: Molecular dissection of the LPA-regulated PC3 cell survival revealed the sequential phosphorylation of Akt, IkappaB, and transcriptional activation of NF-kappaB. Both Akt and NF-kappaB were required to escape serum deprivation-induced cell death since their inhibition abrogated the LPA-mediated PC3 cell survival. Data from archival human tissue show that NF-kappaB is constitutively activated in prostate cancers, but not in benign prostate tissues. CONCLUSIONS: Targeted disruption of the LPA receptor-Akt-NF-kappaB signaling axis may be effective for the treatment of androgen-insensitive prostate cancer.

Duke Scholars

Published In

Prostate

DOI

ISSN

0270-4137

Publication Date

October 1, 2004

Volume

61

Issue

2

Start / End Page

105 / 113

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Male
  • Lysophospholipids
 

Citation

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MLA
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Raj, G. V., Sekula, J. A., Guo, R., Madden, J. F., & Daaka, Y. (2004). Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB. Prostate, 61(2), 105–113. https://doi.org/10.1002/pros.20083
Raj, Ganesh V., Jeffrey A. Sekula, Rishu Guo, John F. Madden, and Yehia Daaka. “Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB.Prostate 61, no. 2 (October 1, 2004): 105–13. https://doi.org/10.1002/pros.20083.
Raj GV, Sekula JA, Guo R, Madden JF, Daaka Y. Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB. Prostate. 2004 Oct 1;61(2):105–13.
Raj, Ganesh V., et al. “Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB.Prostate, vol. 61, no. 2, Oct. 2004, pp. 105–13. Pubmed, doi:10.1002/pros.20083.
Raj GV, Sekula JA, Guo R, Madden JF, Daaka Y. Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB. Prostate. 2004 Oct 1;61(2):105–113.
Journal cover image

Published In

Prostate

DOI

ISSN

0270-4137

Publication Date

October 1, 2004

Volume

61

Issue

2

Start / End Page

105 / 113

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Male
  • Lysophospholipids