Related Experiment Video

Updated: Aug 9, 2026

Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors
07:01

Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors

Published on: March 1, 2020

Check, double check: the G2 barrier to cancer

Floris Foijer1, Hein te Riele

  • 1Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Cell Cycle (Georgetown, Tex.)
|April 22, 2006
PubMed

Insights

Loss of the G1/S checkpoint, critical for cancer, sensitizes cells to apoptosis. Suppressing this cell death leads to G2 arrest, not proliferation, revealing a new barrier to tumor development.

Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • Loss of the G1/S cell cycle checkpoint is a key event in cancer development.
  • Cells lacking retinoblastoma tumor suppressor genes (TKO MEFs) undergo apoptosis under specific conditions.
  • This apoptosis is considered a barrier to uncontrolled cell proliferation.

Purpose of the Study:

  • To investigate the consequences of suppressing apoptosis in cells lacking the G1/S checkpoint.
  • To explore the role of p53 and G2 arrest in preventing oncogenic transformation.
  • To re-evaluate the hypothesis linking G1/S checkpoint loss to cancer progression via apoptosis suppression.

Main Methods:

  • Utilized primary mouse embryonic fibroblasts lacking the retinoblastoma suppressor gene family (TKO MEFs).
  • Experimentally suppressed apoptotic cell death in these cells.
  • Analyzed cell cycle progression, focusing on G1/S and G2 checkpoints.
  • Investigated the role of p53 in mediating cellular responses.

Main Results:

  • Suppression of apoptosis in TKO MEFs did not result in unconstrained proliferation.
  • Instead, cells lacking both G1/S checkpoint and apoptosis control arrested in the G2 phase.
  • This G2 arrest was dependent on the p53 tumor suppressor protein.
  • Alleviation of G2 arrest is proposed as a potential mechanism for tumorigenesis in Rb-deficient cells.

Conclusions:

  • The loss of the G1/S checkpoint alone does not guarantee proliferation due to a p53-dependent G2 arrest.
  • This G2 checkpoint acts as a significant barrier against oncogenic transformation.
  • The interplay between Rb deficiency, apoptosis suppression, and p53-mediated G2 arrest is crucial in cancer development.

More Related Videos

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics11:28

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

Published on: May 11, 2016

Related Concept Videos

Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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...
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...
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.