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A role for cholinesterases in tumorigenesis?
H Soreq1, Y Lapidot-Lifson, H Zakut
1Department of Biological Chemistry, Life Sciences Institute, Hebrew University of Jerusalem, Israel.
Cancer Cells (Cold Spring Harbor, N.Y. : 1989)
|December 1, 1991
Summary
Cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) may link to cancer. Their altered genes and potential phosphorylation by kinases suggest a role in tumor cell proliferation and possible tumorigenic effects from organophosphorous poisons.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) terminate cholinergic signaling.
- Evidence suggests ACHE and BCHE are involved in tumorigenesis.
- Gene amplification, mutation, and aberrant expression of ACHE and BCHE occur in various human tumors.
Purpose of the Study:
- To explore the potential role of cholinesterases in tumor cell proliferation.
- To investigate the link between cholinesterases and cdc2-related protein kinases.
- To discuss the tumorigenic potential of organophosphorous poisons.
Main Methods:
- Analysis of gene expression and chromosomal abnormalities near ACHE and BCHE loci.
- Identification of consensus peptide motifs in ACHE and BCHE.
- Review of existing literature on cholinesterases, kinases, and tumorigenesis.
Main Results:
- ACHE and BCHE genes show amplification and mutation in tumors, with frequent chromosomal abnormalities near their loci.
- Both enzymes possess a peptide motif common to substrates of cdc2-related kinases.
- Phosphorylation by these kinases is a potential mechanism linking cholinesterases to tumor proliferation.
Conclusions:
- Cholinesterases may play a direct role in tumor cell proliferation through kinase-mediated phosphorylation.
- Organophosphorous compounds, by inhibiting cholinesterases, might possess tumorigenic properties.
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