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  • The EMBO Journal (2004) 23, 3303 - 3313
  • doi:10.1038/sj.emboj.7600345

Published online: 29 July 2004

PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase

Frauke Leenders1, Kristin Möpert1, Anett Schmiedeknecht1, Ansgar Santel1, Frank Czauderna1, Manuela Aleku1, Silke Penschuck1,a, Sibylle Dames1, Maria Sternberger1, Thomas Röhl1, Axel Wellmann2, Wolfgang Arnold1, Klaus Giese1, Jörg Kaufmann1 and Anke Klippel1

  1. atugen AG, Berlin, Germany
  2. Pathologisches Institut der Unikliniken, Bonn, Germany

Correspondence to:

Anke Klippel, atugen AG, Robert-Rössle-Str. 10, 13125 Berlin, Germany. Tel.: +49 30 9489 2832; Fax: +49 30 9489 2827; E-mail: klippel@atugen.com

aPresent address: H Lundbeck A/S, Valby, Denmark

Received 18 February 2004; Accepted 5 July 2004

Chronic activation of the phosphoinositide 3-kinase (PI3K)/PTEN signal transduction pathway contributes to metastatic cell growth, but up to now effectors mediating this response are poorly defined. By simulating chronic activation of PI3K signaling experimentally, combined with three-dimensional (3D) culture conditions and gene expression profiling, we aimed to identify novel effectors that contribute to malignant cell growth. Using this approach we identified and validated PKN3, a barely characterized protein kinase C-related molecule, as a novel effector mediating malignant cell growth downstream of activated PI3K. PKN3 is required for invasive prostate cell growth as assessed by 3D cell culture assays and in an orthotopic mouse tumor model by inducible expression of short hairpin RNA (shRNA). We demonstrate that PKN3 is regulated by PI3K at both the expression level and the catalytic activity level. Therefore, PKN3 might represent a preferred target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of PI3K.

  • Keywords:

    • metastasis,
    • orthotopic prostate tumor model,
    • phosphoinositide 3-kinase,
    • PTEN,
    • 3D cell culture
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