Effects of 5-HT1C-receptor expression on cell proliferation control in hamster fibroblasts: serotonin fails to induce a transformed phenotype.
5-HT1c receptors have been shown to act as protooncogenes in NIH 3T3 cells, inducing ligand-dependent focus formation. In order to assess their mitogenic and oncogenic potential in a different cell system, we transfected these receptors into CCL39 hamster fibroblasts, a well-characterized growth factor-dependent cell line. Cell clones expressing functional receptors were isolated and tested for (a) growth factor dependence of proliferation measuring thymidine incorporation in response to varying doses of serum, (b) the response to serotonin alone or in combination with other growth factors, and (c) the capacity for anchorage-independent proliferation. In the absence or presence of serotonin, the large majority of the clones isolated showed normal morphology and normal growth factor dependence and was unable to grow in soft agar. None of the clones showed a significant response to serotonin alone in DNA synthesis reinitiation experiments, but synergy was observed between serotonin and the tyrosine kinase activating growth factors EGF and FGF. However, the major part of this effect could be abolished by an antagonist of 5-HT1b receptors, which are endogenous in CCL39 cells. The same receptor was found to mediate a significant mitogenic response to the neurotransmitter in Ha-ras-transfected cells. The fact that 5-HT1c receptors do not readily induce a transformed phenotype in CCL39 cells clearly distinguishes them from strong dominantly acting oncogene products like RAS, SRC, or FMS.
Kahan
C
C
Centre de Biochimie-CNRS, Université de Nice-Sophia Antipolis, France.
Julius
D
D
Pouysségur
J
J
Seuwen
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012701:Serotonin; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D004247:DNA