Related Experiment Video

Updated: Jun 20, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
09:24

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer

Published on: September 13, 2018

Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer

Fiona M Platt1, Carolyn D Hurst, Claire F Taylor

  • 1Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 1, 2009
PubMed
Abstract

Insights

Alterations in the phosphatidylinositol 3-kinase (PI3K) pathway are common in bladder cancer. The study suggests single-drug therapies targeting this pathway may not be effective due to a lack of redundancy in mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in various cancers.
  • Understanding PI3K pathway alterations is crucial for developing effective targeted therapies in bladder cancer.
  • Predicting treatment efficacy requires detailed knowledge of tumor-specific pathway biology.

Purpose of the Study:

  • To investigate the frequency and distribution of alterations in key PI3K pathway components and their regulators in bladder cancer.
  • To assess mutations, copy number alterations, and gene expression of PIK3CA, PTEN, TSC1, RHEB, and LKB1.
  • To examine upstream regulators like FGFR3 and RAS genes in bladder tumors and cell lines.

Main Methods:

  • Analysis of bladder tumors and cell lines for genetic alterations (mutation, loss of heterozygosity, copy number alteration) and gene expression.
  • Focus on PIK3CA, PTEN, TSC1, RHEB, LKB1, FGFR3, and RAS genes.
  • Statistical assessment of alteration frequencies and distributions.

Main Results:

  • PIK3CA mutations occurred in 25% of tumors, predominantly in the helical domain.
  • PTEN alterations (loss of heterozygosity, deletion, reduced expression) were found in 12% of tumors and 46% of cell lines.
  • TSC1 mutations and 9q loss of heterozygosity were observed in 16% of tumors and 57% of cell lines, respectively. RHEB and LKB1 showed minimal mutations.

Conclusions:

  • PI3K pathway alterations are prevalent in bladder cancer.
  • The independent distribution of these alterations suggests potential additive or synergistic effects.
  • The findings support the use of these characterized cell lines for preclinical testing of targeted agents, but caution against single-agent PI3K-targeted therapy due to lack of redundancy.

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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...
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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...