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Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures
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Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase

Sohye Kang1, Adam Denley, Bart Vanhaesebroeck

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 239, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 25, 2006
PubMed

Insights

Wild-type Class I phosphoinositide 3-kinase (PI3K) isoforms p110beta, -gamma, and -delta exhibit oncogenic potential, unlike p110alpha. This suggests differential expression of PI3K isoforms contributes to cancer development.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Class I phosphoinositide 3-kinase (PI3K) is crucial in cell signaling.
  • PI3K comprises four catalytic subunits: p110alpha, -beta, -gamma, and -delta.
  • While p110alpha mutations are linked to cancer, the oncogenic potential of other isoforms is less understood.

Purpose of the Study:

  • To investigate the oncogenic potential of wild-type Class I PI3K isoforms.
  • To explore the signaling pathways and upstream regulators involved in PI3K-mediated cell transformation.

Main Methods:

  • Cell transformation assays were performed using wild-type p110beta, -gamma, and -delta isoforms.
  • The role of kinase activity was assessed using rapamycin, a target of rapamycin inhibitor.
  • Upstream signaling requirements, including Ras dependency, were analyzed.

Main Results:

  • Wild-type p110beta, -gamma, and -delta isoforms induced cell transformation.
  • Oncogenic potential required kinase activity and was inhibited by rapamycin.
  • p110delta constitutively activated Akt, while p110gamma required serum.
  • Transforming activity of p110gamma and potentially p110beta depended on Ras, whereas p110delta showed Ras-independent potential.

Conclusions:

  • Wild-type non-alpha PI3K isoforms possess intrinsic oncogenic potential.
  • Differential expression of these isoforms may contribute to cancer development.
  • Understanding these pathways could reveal new therapeutic targets.

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