Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4703-7.

Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.

Author information

  • 1Laboratory of Cellular Development and Oncology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.

Abstract

We have evaluated the muscarinic acetylcholine family of G protein-coupled receptors (mAChRs) for their oncogenic potential. These receptors are preferentially expressed in postmitotic cells, transducing signals specified by their endogenous agonist, the neurotransmitter acetylcholine. Cells transfected with individual human mAChR genes were morphologically indistinguishable from parental NIH 3T3 cells in the absence of agonist. In contrast, when cultures were supplemented with carbachol, a stable analog of acetylcholine, foci of transformation readily appeared in m1, m3, or m5 but not in m2 or m4 mAChRs transfectants. Receptor expression was verified by ligand binding and was similar for each transfected culture. Transformation was dose-dependent and required only low levels of receptor expression. In transformation-competent cells, agonist induced phosphatidylinositol hydrolysis, whereas in m2 or m4 transfectants, receptors were coupled to the inhibition of adenylyl cyclase. These findings demonstrate that mAChRs linked to phosphatidylinositol hydrolysis can act as conditional oncogenes when expressed in cells capable of proliferation.

PMID:
1905013
[PubMed - indexed for MEDLINE]
PMCID:
PMC51734
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk