Related Experiment Video

Updated: Oct 17, 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

Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition

K Ichimura1, M B Bolin, H M Goike

  • 1Department of Pathology, University of Cambridge, Addenbrooke's Hospital, United Kingdom.

Cancer Research
|February 10, 2000
PubMed

Insights

Deregulation of the cell cycle

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cell cycle deregulation, particularly at the G1-S transition, is a hallmark of human tumors like astrocytic gliomas.
  • Previous studies identified G1-S transition control abnormalities in glioblastomas (GBs).
  • The p14ARF/MDM2/p53 pathway is implicated in cellular response to abnormal cell cycle entry.

Purpose of the Study:

  • To investigate the roles of G1-S transition control and the p14ARF/MDM2/p53 pathway in astrocytic glioma development.
  • To examine gene abnormalities within these regulatory pathways across different grades of astrocytic gliomas.

Main Methods:

  • Analysis of gene abnormalities (mutation, deletion, amplification) in RB1, CDKN2A, CDKN2B, CDK4, TP53, MDM2, and p14ARF.
  • Study included 190 primary human astrocytic gliomas: 136 GBs, 39 anaplastic astrocytomas (AAs), and 15 astrocytomas (As).

Main Results:

  • 67% of GBs and 21% of AAs showed G1-S control abnormalities.
  • 76% of GBs, 72% of AAs, and 67% of As exhibited a deregulated p53 pathway.
  • 96% of GBs and 88% of AAs with abnormal G1-S control also had a deregulated p53 pathway.

Conclusions:

  • Deregulation of G1-S transition control is frequently accompanied by p53 pathway inactivation in astrocytic gliomas.
  • These two systems cooperate in the development and progression of primary human astrocytic gliomas.

More Related Videos

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells12:52

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Published on: November 28, 2015

Related Concept Videos

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...