Related Experiment Videos

Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a

Scott A Christopher1, Paula Diegelman, Carl W Porter

  • 1Fox Chase Cancer Center, Division of Population Science, Philadelphia, Pennsylvania 19111, USA.

Cancer Research
|November 20, 2002
PubMed

Insights

Methylthioadenosine phosphorylase (MTAP) acts as a tumor suppressor by reducing polyamine levels. Restoring MTAP in cancer cells inhibits tumor growth and anchorage-independent colony formation.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • The methylthioadenosine phosphorylase (MTAP) gene is frequently deleted in various human tumors.
  • MTAP salvages methylthioadenosine, a byproduct of polyamine metabolism.
  • Understanding MTAP's role is crucial for cancer research.

Purpose of the Study:

  • To investigate the tumor suppressor activity of MTAP.
  • To determine the mechanism by which MTAP affects tumorigenicity.
  • To explore the link between MTAP and polyamine metabolism in cancer cells.

Main Methods:

  • Reintroduction of MTAP into MCF-7 breast adenocarcinoma cells.
  • Assessment of cell growth, colony formation in soft agar/collagen, and tumor formation in SCID mice.
  • Analysis of intracellular polyamine levels and enzymatic activity of MTAP.

Main Results:

  • MTAP expression suppressed anchorage-independent growth and tumor formation in vivo.
  • MTAP's enzymatic activity was essential for its tumor-suppressive effects.
  • MTAP expression led to decreased intracellular polyamine levels and altered polyamine ratios.

Conclusions:

  • MTAP exhibits significant tumor suppressor activity.
  • The tumor suppressor function of MTAP is likely mediated by its impact on intracellular polyamine pools.
  • MTAP represents a potential therapeutic target in cancers with MTAP deletion.

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...
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...
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...
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...