Conventional approaches to identifying cancer targets are complicated by the chromosomal instability of tumour cells, and typically result in a large number of differentially expressed candidate genes with uncertain disease relevance. Here we present a novel approach which aims to elucidate the molecular changes that are induced after loss of tumour suppressor function. Using gene silencing tools, we mimic the loss of tumour suppressor function to identify key regulators of tumour initiation and progression. Loss of function of the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) correlates with increased invasive cell growth due to the resulting chronic activation of the PI 3-kinase (phosphoinositide 3-kinase) pathway. Induced activation of PI 3-kinase either by inhibiting PTEN expression or by using p110*, a constitutively active PI 3-kinase, increased signalling and the invasive growth potential of cells. Using this unbiased approach we have identified novel downstream effectors of PI 3-kinase/PTEN signalling that mediate the behaviour of cells with a hyperactive PI 3-kinase pathway. These molecules represent candidate targets for therapeutic intervention in patients with PTEN-deficient tumours.
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April 2004
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Conference Article|
April 01 2004
Identification of novel effectors of invasive cell growth downstream of phosphoinositide 3-kinase
J. Kaufmann;
J. Kaufmann
atugen AG, Robert Rössle Strasse 10, 13125 Berlin, Germany
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G. Pronk;
G. Pronk
atugen AG, Robert Rössle Strasse 10, 13125 Berlin, Germany
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K. Giese;
K. Giese
atugen AG, Robert Rössle Strasse 10, 13125 Berlin, Germany
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A. Klippel
A. Klippel
1
atugen AG, Robert Rössle Strasse 10, 13125 Berlin, Germany
1To whom correspondence should be addressed (e-mail klippel@atugen.com).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (2): 355–359.
Citation
J. Kaufmann, G. Pronk, K. Giese, A. Klippel; Identification of novel effectors of invasive cell growth downstream of phosphoinositide 3-kinase. Biochem Soc Trans 1 April 2004; 32 (2): 355–359. doi: https://doi.org/10.1042/bst0320355
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