Related Experiment Video

Updated: Aug 21, 2026

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

PAkt, cyclin D1 and p27/Kip.1 in glioblastomas with and without EGFR amplification and PTEN mutation

Valentina Fiano1, Chiara Ghimenti, Sara Imarisio

  • 1Department of Neuroscience, University of Turin, Via Cherasco, 15 and Turin, Italy.

Anticancer Research
|November 3, 2004
PubMed
Abstract

Insights

The PI3K/Akt pathway influences glioblastoma cell cycle regulators. Cyclin D1 expression correlates with Akt activity, while p27 Kip.1 expression is less dependent on PTEN and EGFR status.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • The phosphoinositide 3-kinase (PI3K)/Akt pathway is crucial for cell growth and survival.
  • Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) activates Akt, inhibiting Forkhead box O (FOXO) transcription factors and influencing cell cycle regulators like p27 Kip.1 and cyclin D1.
  • PTEN negatively regulates Akt by degrading PIP3, while Epidermal Growth Factor Receptor (EGFR) can activate PI3K signaling. Glioblastomas frequently exhibit PTEN mutations and EGFR amplification.

Purpose of the Study:

  • To investigate the relationship between PTEN mutations, EGFR amplification, and key cell cycle regulators (p27 Kip.1, cyclin D1) in glioblastoma.
  • To explore the role of Akt activation in modulating these cell cycle proteins within the tumor microenvironment.

Main Methods:

  • Analysis of PTEN mutation and EGFR amplification using Polymerase Chain Reaction (PCR).
  • Assessment of Akt, p27 Kip.1, and cyclin D1 expression via immunohistochemistry.
  • Evaluation of apoptosis and proliferation using TUNEL and MIB-1 labeling in 65 glioblastoma samples.

Main Results:

  • EGFR amplification and PTEN mutations were observed in 50% and 30% of glioblastomas, respectively.
  • No significant correlation was found between EGFR amplification or PTEN mutation status and the expression of p27 Kip.1 or cyclin D1.
  • Cyclin D1 expression showed a positive association with Akt-expressing areas (69%), whereas p27 Kip.1 expression was less frequent (30%).

Conclusions:

  • Cyclin D1 and p27 Kip.1 expression are more directly linked to Akt activity than to PTEN or EGFR alterations in glioblastomas.
  • These findings highlight the complex interplay of signaling pathways regulating cell cycle progression in glioblastoma.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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 Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...