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Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation
D Julius1, T J Livelli, T M Jessell
1Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Abstract:
Neurotransmitter receptors are usually restricted to neuronal cells, but the signaling pathways activated by these receptors are widely distributed in both neural and non-neural cells. The functional consequences of activating a brain-specific neurotransmitter receptor, the serotonin 5HT1c receptor, in the unnatural environment of a fibroblast were examined. Introduction of functional 5HT1c receptors into NIH 3T3 cells results, at high frequency, in the generation of transformed foci. Moreover, the generation and maintenance of transformed foci requires continued activation of the serotonin receptor. In addition, the injection of cells derived from transformed foci into nude mice results in the generation of tumors. The serotonin 5HT1c receptor therefore functions as a protooncogene when expressed in NIH 3T3 fibroblasts.
Insights
Introducing serotonin 5HT1c receptors into fibroblasts transformed them, acting as a protooncogene. Continued receptor activation was necessary for maintaining this cancerous state and tumor formation in mice.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Neurotransmitter receptors are typically confined to neurons, but their downstream signaling pathways are present in various cell types.
- The serotonin 5HT1c receptor is a brain-specific neurotransmitter receptor.
Purpose of the Study:
- To investigate the functional consequences of expressing the serotonin 5HT1c receptor in non-neuronal cells (fibroblasts).
- To determine if the serotonin 5HT1c receptor can act as a protooncogene in fibroblasts.
Main Methods:
- Introduction of functional serotonin 5HT1c receptors into NIH 3T3 fibroblast cells.
- Observation of transformed foci generation and maintenance.
- Tumorigenicity assessment by injecting transformed cells into nude mice.
Main Results:
- Expression of serotonin 5HT1c receptors in NIH 3T3 cells led to the frequent generation of transformed foci.
- Continued activation of the serotonin receptor was essential for the sustained transformation.
- Cells derived from transformed foci formed tumors when implanted in nude mice.
Conclusions:
- The serotonin 5HT1c receptor functions as a protooncogene when expressed in NIH 3T3 fibroblasts.
- This study demonstrates the oncogenic potential of a neuronal receptor in a non-neuronal context.