The role of PI 3-kinase p110β in AKT signally, cell survival, and proliferation in human prostate cancer cells

Karen M. Hill, Sara Kalifa, Jharna R. Das, Tahira Bhatti, Martha Gay, Danielle Williams, La Tonia Taliferro-Smith, Angelo M. De Marzo

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


BACKGROUND. Class IA PI 3-kinases produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 is bound by AKT which facilities its activation by PDK1. Activated AKT promotes cell survival and stimulates cell proliferation. Class IA PI 3-kinases are heterodimers consisting of a regulatory subunit p85 and a catalytic subunit p110. The p110α isoform has been shown to be mutated in a number of tumor types. A number of recent studies suggest that the p110β isoform may be functionally relevant in prostate cancer. In this study we extend this work to include the examination of the expression and functional properties of p110α and p110β in three different prostate cancer cell lines, DU145, LNCaP, PC3, as well as the non-tumorigenic but immortalized RWPE1 prostate epithelial cell line. METHODS. Western blot analysis was used to measure protein expression and quantitative real-time PCR was used to measure mRNA levels. After targeted knockdown using isoformspecific siRNAs to reduce PI 3-kinase p110α or p110β isoform expression, we measured downstream signally events such as phosphorylation of AKT, ERK 1/2, PDK, and FOXO, as well as biological consequences such as changes in apoptosis, and alterations in cell cycle progression. RESULTS. In all three prostate cancer cell lines examined, targeted knockdown of p110β, and not p110α, resulted in significantly reduced AKT, PDK, and FOXO phosphorylation. While knockdown of either p110 isoform resulted in an increase in apoptosis and a cell cycle arrest in G1 in the remaining non-apoptotic cells, these effects were much more pronounced with knockdown of p110β. CONCLUSIONS. Our results support the concept that p110β appears to be the predominant functional class I PI 3-kinase isoform in prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)755-764
Number of pages10
Issue number7
StatePublished - May 15 2010


  • AKT
  • FOXO
  • PI 3-kinase
  • Prostate cancer
  • p110α
  • p110β

ASJC Scopus subject areas

  • Oncology
  • Urology


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