The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion

X. Wu, T. Obata, Q. Khan, R. A. Highshaw, Ralph W deVere White, Colleen A Sweeney

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


OBJECTIVES: To investigate the role of the phosphatidylinositol (PI)-3 kinase pathway in the invasion of bladder cancer cell lines, and to assess the activation of this pathway in primary human bladder tumours. MATERIALS AND METHODS: Human bladder cancer cells were treated with pathway specific inhibitors or were transfected with PI-3 kinase pathway components. The invasion of cultured bladder cancer cells was analysed by an invasion assay. Bladder cancer cells lines and primary human bladder tumours were analysed for pathway activation by western blotting. RESULTS: A specific inhibitor of PI-3 kinase enzyme activity, Ly294002, potently suppressed the invasive properties of three highly invasive bladder tumour cell lines. Restoration of the PTEN gene to invasive UM-UC-3 bladder tumour cells or expression of a dominant-negative version of the PI-3 kinase target, Akt, also potently inhibited invasion, indicating a central role for the PI-3 kinase/Akt pathway in this process. In addition, 55% of primary tumours from patients with bladder cancer had markedly high levels of phosphorylated Akt. CONCLUSION: Pharmacological or biochemical inhibition of the PI-3 kinase pathway drastically reduced the invasive capacity of bladder cancer cell lines; over half of primary human bladder tumours had high Akt phosphorylation, suggesting that the aberrant activation of this pathway may contribute to the invasion of a significant subset of bladder cancers.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalBJU International
Issue number1
StatePublished - Jan 2004


  • Bladder cancer
  • Invasion
  • PI-3 kinase
  • PTEN

ASJC Scopus subject areas

  • Urology


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