Ornithine decarboxylase gene expression is aberrantly regulated via the cAMP signal transduction pathway in malignant

R A Hurta1, J A Wright

  • 1Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.

Insights

H-ras transformed cells show altered ornithine decarboxylase (ODC) gene expression, a key enzyme in polyamine synthesis. These changes are linked to specific signaling pathways, particularly those involving cyclic AMP (cAMP).

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Ornithine decarboxylase (ODC) is a critical enzyme in polyamine biosynthesis.
  • Polyamines are essential for cell growth and proliferation.
  • H-ras transformation can alter cellular signaling pathways.

Purpose of the Study:

  • To investigate alterations in signal pathways controlling ornithine decarboxylase (ODC) expression in H-ras transformed cells.
  • To determine the role of cyclic AMP (cAMP) signaling in ODC regulation in these cells.

Main Methods:

  • Treatment of mouse 10T1/2 fibroblasts and H-ras transformed cell lines with cAMP synthesis stimulators (forskolin, cholera toxin), a cAMP analogue (8-bromo-cAMP), and a cAMP degradation inhibitor (3-isobutyl-1-methylxanthine).
  • Assessment of ODC gene expression using techniques including Actinomycin D and cycloheximide treatments.
  • Investigation of the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA).

Main Results:

  • H-ras transformed cells exhibited elevated ODC gene expression compared to parental cells.
  • Forskolin and cholera toxin significantly increased ODC expression in a cAMP-dependent manner.
  • Actinomycin D indicated transcriptional involvement in forskolin-mediated ODC elevation.
  • Cycloheximide differentially affected ODC levels in malignant versus benign H-ras transformed cells.
  • TPA also led to increased ODC mRNA levels in H-ras transformed cells.

Conclusions:

  • H-ras transformation alters signal pathways controlling ODC expression.
  • cAMP signaling plays a significant role in regulating ODC in H-ras transformed cells.
  • Transcriptional and translational mechanisms are involved in ODC dysregulation in cancer cells.

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
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...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...