Related Experiment Video

Updated: Jun 1, 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

Genetic aberrations leading to MAPK pathway activation mediate oncogene-induced senescence in sporadic pilocytic

Karine Jacob1, Dongh-Anh Quang-Khuong, David T W Jones

  • 1Department of Human Genetics, McGill University Health Center Research Institute, Montreal, Canada.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 26, 2011
PubMed
Abstract

Insights

Oncogene-induced senescence (OIS) is triggered in pilocytic astrocytomas (PA) via MAPK pathway activation. This senescence mechanism explains the slow growth and favorable prognosis of these pediatric brain tumors.

Area of Science:

  • Oncology
  • Cell Biology
  • Neuro-oncology

Background:

  • Pilocytic astrocytomas (PA) are common pediatric brain tumors.
  • The mitogen-activated protein kinase (MAPK) pathway is frequently altered in PA.
  • Oncogenic BRAF/Ras or NF1 loss can activate the MAPK pathway and potentially induce oncogene-induced senescence (OIS).

Purpose of the Study:

  • To investigate whether OIS is induced in pilocytic astrocytomas.
  • To determine the role of the MAPK pathway and p16(INK4a) in OIS within PA.

Main Methods:

  • Analysis of senescence markers in three independent PA cohorts.
  • In vitro studies using astrocytic cell lines with forced expression of BRAF.
  • Assessment of OIS induction and the role of p16(INK4a) in immortalized astrocytes.

Main Results:

  • PAs exhibit significant OIS markers, including senescence-associated β-galactosidase activity and p16(INK4a) induction in 88.5% of samples.
  • Senescence-associated gene expression was confirmed at the mRNA level in PA tumor series.
  • In vitro, BRAF activation induced OIS in astrocytes, and p16(INK4a) loss abrogated this effect.

Conclusions:

  • OIS is a key mechanism in pilocytic astrocytomas, induced by aberrant MAPK activation.
  • OIS likely contributes to the characteristic slow growth and favorable prognosis of PA.
  • The p16(INK4a) pathway is crucial for mediating OIS in astrocytes within the context of PA.

More Related Videos

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

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...
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...
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...
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 Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...