Connexin43 pseudogene is expressed in tumor cells and inhibits growth

Mustapha Kandouz1, Andrew Bier, George D Carystinos

  • 1Department of Oncology, Montréal Centre for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada H3T 1E2.

Oncogene
|May 4, 2004
PubMed

Insights

The Connexin43 (Cx43) pseudogene (PsiCx43) is transcribed and translated into a protein in cancer cells, inhibiting their growth. This pseudogene does not affect gap junction communication, expanding the known functional pseudogenes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Pseudogenes are DNA sequences typically considered nonfunctional.
  • Gap junctions, formed by connexins, facilitate intercellular communication and are often deregulated in cancer.
  • Connexin43 (Cx43) is the only connexin with a reported pseudogene, PsiCx43.

Purpose of the Study:

  • To investigate the functional potential of the Cx43 pseudogene (PsiCx43).
  • To determine if PsiCx43 is transcribed and translated in cancer cells.
  • To assess the functional significance of PsiCx43 in cancer cell behavior.

Main Methods:

  • Detection of PsiCx43 mRNA transcripts in cancer cell lines and normal mammary epithelial cells.
  • In vitro translation assay to assess PsiCx43 protein production.
  • Expression of a PsiCx43-green fluorescence protein fusion in MCF-7 cells.
  • MTT growth, colony formation, and scrape-loading assays to evaluate functional impact.

Main Results:

  • PsiCx43 mRNA transcripts were identified in cancer cell lines but not in normal cells.
  • The PsiCx43 coding plasmid was translated into a 43 kDa protein in vitro.
  • Expression of PsiCx43 led to significant growth inhibition in cancer cells.
  • PsiCx43 did not affect gap junctional intercellular communication.

Conclusions:

  • PsiCx43 is a functionally transcribed and translated pseudogene.
  • PsiCx43 exhibits growth inhibitory properties in cancer cells.
  • This finding expands the known repertoire of functional pseudogenes.

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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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...
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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...