Related Experiment Video

Updated: Aug 8, 2026

Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
09:51

Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress

Published on: May 7, 2014

Diminished G1 checkpoint after gamma-irradiation and altered cell cycle regulation by insulin-like growth factor II

L Zhang1, M Kim, Y H Choi

  • 1Molecular Oncology Section, National Institutes of Health, Bethesda, Maryland 20892-1928, USA.

The Journal of Biological Chemistry
|May 1, 1999
PubMed

Insights

Insulin-like growth factor II (IGFII) overexpression accelerates cell cycling and weakens the G1 checkpoint after DNA damage. This contributes to increased tumor growth and genetic alterations in cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • High insulin-like growth factor II (IGFII) mRNA expression is observed in various human tumors.
  • IGFII's role in tumorigenesis, particularly in rhabdomyosarcoma, warrants investigation.

Purpose of the Study:

  • To investigate the impact of IGFII overexpression on cell cycle regulation and growth.
  • To determine if IGFII influences the DNA damage response.

Main Methods:

  • Comparison of mouse myoblast cell lines (C2C12) with and without stable IGFII overexpression.
  • Utilized a rhabdomyosarcoma cell line (RH30) with high IGFII expression.
  • Developed a Chinese hamster ovary (CHO) cell line with tetracycline-controlled IGFII expression.
  • Assessed cell cycle progression and checkpoint activation after gamma-irradiation and methylmethane sulfonate (MMS) treatment.

Main Results:

  • IGFII overexpression in C2C12 cells led to reduced cycling time and increased growth rate.
  • Cells with IGFII overexpression exhibited a diminished G1 checkpoint and an extended G2/M arrest after DNA damage.
  • IGFII overexpression correlated with increased cyclin D1, p21, and p53 protein levels, and elevated mitogen-activated protein kinase activity.
  • CHO cells with high IGFII expression showed a shortened cell cycle and a diminished G1 checkpoint after MMS treatment.

Conclusions:

  • IGFII overexpression shortens cell cycling time and impairs the G1 checkpoint following DNA damage.
  • These effects occur despite intact p53/p21 induction, suggesting alternative regulatory pathways.
  • IGFII-associated alterations in cell cycle components may promote high growth rates and genetic instability in tumors.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry08:21

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

Related Concept Videos

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.
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...
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...
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...
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...
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...