Related Experiment Video

Updated: Aug 20, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic

Sohye Kang1, Andreas G Bader, Peter K Vogt

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 14, 2005
PubMed

Insights

Common cancer gene mutations in phosphatidyl-inositol 3-kinase (PI3-kinase) drive oncogenic transformation. These PI3-kinase mutations activate downstream signaling, making them targets for new anticancer drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mutations in the phosphatidyl-inositol 3-kinase (PI3-kinase) pathway are prevalent in human cancers.
  • Specific somatic mutations in the PIK3CA gene are frequently observed in tumors, indicating a potential oncogenic role.

Purpose of the Study:

  • To investigate the growth-regulatory and signaling properties of three common PI3-kinase mutations (E542K, E545K, H1047R).
  • To assess the potential of mutated PI3-kinase as a therapeutic target for cancer treatment.

Main Methods:

  • Expressed PI3-kinase mutants (E542K, E545K, H1047R) in chicken embryo fibroblasts.
  • Performed in vitro kinase assays to measure catalytic activity.
  • Analyzed constitutive phosphorylation of downstream signaling proteins (Akt, p70 S6 kinase, 4E-binding protein 1).
  • Assessed the effect of the target of rapamycin (TOR) inhibitor, rapamycin, on cellular transformation.

Main Results:

  • All three PI3-kinase mutants induced efficient oncogenic transformation in fibroblasts.
  • Mutant transformation correlated with increased catalytic activity.
  • Mutant-transformed cells exhibited constitutive phosphorylation of Akt, p70 S6 kinase, and 4E-binding protein 1.
  • Rapamycin significantly inhibited transformation mediated by PI3-kinase mutants.

Conclusions:

  • Mutated PI3-kinase proteins possess potent oncogenic transforming activity.
  • The target of rapamycin (TOR) pathway is essential for PI3-kinase-driven transformation.
  • Mutated PI3-kinase represents a promising target for developing specific small molecule inhibitors for cancer therapy.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...