Abstract
We report the isolation and characterization of a serotoninergic cell line, 1C11, derived from a mouse teratocarcinoma. The clone 1C11 was immortalized through the expression of the simian virus 40 oncogenes. 1C11 presents two states: an immature epithelial-like state (1C11 precursor) and a more differentiated state (1C11). After induction by dibutyryl cyclic AMP and cyclohexanecarboxylic acid, almost 100% of 1C11 cells continue to divide and have acquired a neural-like phenotype. 1C11* cells coexpress several neural markers, such as synaptophysin (the membrane constituent of synaptic vesicles), the neuropeptide [Met5]enkephalin, and the neurotransmitter serotonin. 1C11* cells store endogenous serotonin and are able to synthesize serotonin from L-tryptophan and to catabolize it by monoamine oxidase B. Moreover, the cells take up serotonin by a carrier-mediated mechanism very similar to that of serotoninergic neurons. The expression of the simian virus 40 oncogenes, which promoted immortalization, does not therefore prevent further differentiation. This inducible cell line constitutes a valuable model for cellular and molecular studies concerning the physiology and the pharmacological modulation of the serotoninergic phenotype.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amano T., Richelson E., Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). Proc Natl Acad Sci U S A. 1972 Jan;69(1):258–263. doi: 10.1073/pnas.69.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Augusti-Tocco G., Sato G. Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc Natl Acad Sci U S A. 1969 Sep;64(1):311–315. doi: 10.1073/pnas.64.1.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beevers S. J., Knowles R. G., Pogson C. I. A sensitive radiometric assay for tryptophan hydroxylase applicable to crude extracts. J Neurochem. 1983 Mar;40(3):894–897. doi: 10.1111/j.1471-4159.1983.tb08066.x. [DOI] [PubMed] [Google Scholar]
- Berstine E. G., Hooper M. L., Grandchamp S., Ephrussi B. Alkaline phosphatase activity in mouse teratoma. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3899–3903. doi: 10.1073/pnas.70.12.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biedler J. L., Roffler-Tarlov S., Schachner M., Freedman L. S. Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res. 1978 Nov;38(11 Pt 1):3751–3757. [PubMed] [Google Scholar]
- Costa J. L., Murphy D. L., Kafka M. S. Demonstration and evaluation of apparent cytoplasmic and vesicular serotonin compartments in human platelets. Biochem Pharmacol. 1977 Mar 15;26(6):517–521. doi: 10.1016/0006-2952(77)90327-6. [DOI] [PubMed] [Google Scholar]
- Covault J., Sanes J. R. Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4544–4548. doi: 10.1073/pnas.82.13.4544. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Da Prada M., Cesura A. M., Launay J. M., Richards J. G. Platelets as a model for neurones? Experientia. 1988 Feb 15;44(2):115–126. doi: 10.1007/BF01952193. [DOI] [PubMed] [Google Scholar]
- Debons-Guillemin M. C., Launay J. M., Roseto A., Périès J. Serotonin and histamine production by human carcinoid cells in culture. Cancer Res. 1982 Apr;42(4):1513–1516. [PubMed] [Google Scholar]
- Furmanski P., Silverman D. J., Lubin M. Expression of differentiated functions in mouse neuroblastoma mediated by dibutyryl-cyclic adenosine monophosphate. Nature. 1971 Oct 8;233(5319):413–415. doi: 10.1038/233413a0. [DOI] [PubMed] [Google Scholar]
- Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grimaud J. A., Druguet M., Peyrol S., Chevalier O., Herbage D., El Badrawy N. Collagen immunotyping in human liver: light and electron microscope study. J Histochem Cytochem. 1980 Nov;28(11):1145–1156. doi: 10.1177/28.11.7000887. [DOI] [PubMed] [Google Scholar]
- Guicheney P., Soliman H., Launay J. M., Dreux C., Meyer P. Circulating monoamine oxidase B and phenolsulfotransferase activities in essential hypertensive patients. Clin Exp Hypertens A. 1988;10(4):533–544. doi: 10.3109/10641968809033907. [DOI] [PubMed] [Google Scholar]
- Gurwitz D., Cunningham D. D. Thrombin modulates and reverses neuroblastoma neurite outgrowth. Proc Natl Acad Sci U S A. 1988 May;85(10):3440–3444. doi: 10.1073/pnas.85.10.3440. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haimart M., Launay J. M., Zürcher G., Cauet N., Dreux C., Da Prada M. Simultaneous determination of histamine and N alpha-methylhistamine in biological samples by an improved enzymatic single isotope assay. Agents Actions. 1985 Apr;16(3-4):71–75. doi: 10.1007/BF01983104. [DOI] [PubMed] [Google Scholar]
- Jones-Villeneuve E. M., McBurney M. W., Rogers K. A., Kalnins V. I. Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells. J Cell Biol. 1982 Aug;94(2):253–262. doi: 10.1083/jcb.94.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellermann O., Buc-Caron M. H., Gaillard J. Immortalization of precursors of endodermal, neuroectodermal and mesodermal lineages, following the introduction of the simian virus (SV40) early region into F9 cells. Differentiation. 1987;35(3):197–205. doi: 10.1111/j.1432-0436.1987.tb00169.x. [DOI] [PubMed] [Google Scholar]
- Kellermann O., Kelly F. Immortalization of early embryonic cell derivatives after the transfer of the early region of simian virus 40 into F9 teratocarcinoma cells. Differentiation. 1986;32(1):74–81. doi: 10.1111/j.1432-0436.1986.tb00558.x. [DOI] [PubMed] [Google Scholar]
- Krystosek A. Neurite formation by neuroblastoma-glioma hybrid cells (NG108-15) in defined medium: stochastic initiation with persistence of differentiated functions. J Cell Physiol. 1985 Nov;125(2):319–329. doi: 10.1002/jcp.1041250222. [DOI] [PubMed] [Google Scholar]
- Kuff E. L., Fewell J. W. Induction of neural-like cells and acetylcholinesterase activity in cultures of F9 teratocarcinoma treated with retinoic acid and dibutyryl cyclic adenosine monophosphate. Dev Biol. 1980 Jun 1;77(1):103–115. doi: 10.1016/0012-1606(80)90459-5. [DOI] [PubMed] [Google Scholar]
- Laubscher A., Pletscher A. Uptake of 5-hydroxytryptamine in blood platelets and its inhibition by drugs: role of plasma membrane and granular storage. J Pharm Pharmacol. 1979 May;31(5):284–289. doi: 10.1111/j.2042-7158.1979.tb13502.x. [DOI] [PubMed] [Google Scholar]
- Lauder J. M., Wallace J. A., Krebs H., Petrusz P., McCarthy K. In vivo and in vitro development of serotonergic neurons. Brain Res Bull. 1982 Jul-Dec;9(1-6):605–625. doi: 10.1016/0361-9230(82)90165-4. [DOI] [PubMed] [Google Scholar]
- Liesi P., Rechardt L., Wartiovaara J. Nerve growth factor induces adrenergic neuronal differentiation in F9 teratocarcinoma cells. Nature. 1983 Nov 17;306(5940):265–267. doi: 10.1038/306265a0. [DOI] [PubMed] [Google Scholar]
- Lorez H. P., Da Prada M., Rendu F., Pletscher A. Mepacrine, a tool for investigating the 5-hydroxytryptamine organelles of blood platelets by fluorescence microscopy. J Lab Clin Med. 1977 Jan;89(1):200–206. [PubMed] [Google Scholar]
- Milstein C., Wright B., Cuello A. C. The discrepancy between the cross-reactivity of a monoclonal antibody to serotonin and its immunohistochemical specificity. Mol Immunol. 1983 Jan;20(1):113–123. doi: 10.1016/0161-5890(83)90110-4. [DOI] [PubMed] [Google Scholar]
- Montano X., Lane D. P. Monoclonal antibody to simian virus 40 small t. J Virol. 1984 Sep;51(3):760–767. doi: 10.1128/jvi.51.3.760-767.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Navone F., Jahn R., Di Gioia G., Stukenbrok H., Greengard P., De Camilli P. Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2511–2527. doi: 10.1083/jcb.103.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peyriéras N., Louvard D., Jacob F. Characterization of antigens recognized by monoclonal and polyclonal antibodies directed against uvomorulin. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8067–8071. doi: 10.1073/pnas.82.23.8067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeiffer S. E., Jakob H., Mikoshiba K., Dubois P., Guenet J. L., Nicolas J. F., Gaillard J., Chevance G., Jacob F. Differentiation of a teratocarcinoma line: preferential development of cholinergic neurons. J Cell Biol. 1981 Jan;88(1):57–66. doi: 10.1083/jcb.88.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross J., Olmsted J. B., Rosenbaum J. L. The ultrastructure of mouse neuroblastoma cells in tissue culture. Tissue Cell. 1975;7(1):107–135. doi: 10.1016/s0040-8166(75)80010-3. [DOI] [PubMed] [Google Scholar]
- Schubert D., Humphreys S., Baroni C., Cohn M. In vitro differentiation of a mouse neuroblastoma. Proc Natl Acad Sci U S A. 1969 Sep;64(1):316–323. doi: 10.1073/pnas.64.1.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seeds N. W., Gilman A. G., Amano T., Nirenberg M. W. Regulation of axon formation by clonal lines of a neural tumor. Proc Natl Acad Sci U S A. 1970 May;66(1):160–167. doi: 10.1073/pnas.66.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sharma S., Notter M. F. Characterization of neurotransmitter phenotype during neuronal differentiation of embryonal carcinoma cells. Dev Biol. 1988 Feb;125(2):246–254. doi: 10.1016/0012-1606(88)90208-4. [DOI] [PubMed] [Google Scholar]
- Tamir H., Liu K. P., Payette R. F., Hsiung S. C., Adlersberg M., Nunez E. A., Gershon M. D. Human medullary thyroid carcinoma: characterization of the serotonergic and neuronal properties of a neurectodermally derived cell line. J Neurosci. 1989 Apr;9(4):1199–1212. doi: 10.1523/JNEUROSCI.09-04-01199.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thibault J., Vidal D., Gros F. In vitro translation of mRNA from rat pheochromocytoma tumors, characterization of tyrosine hydroxylase. Biochem Biophys Res Commun. 1981 Apr 15;99(3):960–968. doi: 10.1016/0006-291x(81)91256-0. [DOI] [PubMed] [Google Scholar]
- Walker R. F., Friedman D. W., Jimenez A. A modified enzymatic-isotopic microassay for serotonin (5HT) using 5HT-N-acetyltransferase partially purified from Drosophila. Life Sci. 1983 Nov 7;33(19):1915–1924. doi: 10.1016/0024-3205(83)90676-8. [DOI] [PubMed] [Google Scholar]
- Westlund K. N., Denney R. M., Kochersperger L. M., Rose R. M., Abell C. W. Distinct monoamine oxidase A and B populations in primate brain. Science. 1985 Oct 11;230(4722):181–183. doi: 10.1126/science.3875898. [DOI] [PubMed] [Google Scholar]
- Wiedenmann B., Franke W. W., Kuhn C., Moll R., Gould V. E. Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A. 1986 May;83(10):3500–3504. doi: 10.1073/pnas.83.10.3500. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoffe J. R., Borchardt R. T. Characterization of serotonin uptake in cultured pheochromocytoma cells. Comparison with norepinephrine uptake. Mol Pharmacol. 1982 Mar;21(2):368–373. [PubMed] [Google Scholar]