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. 1991 Nov 15;88(22):9994–9998. doi: 10.1073/pnas.88.22.9994

Insulin-like growth factor I shifts from promoting cell division to potentiating maturation during neuronal differentiation.

S Påhlman 1, G Meyerson 1, E Lindgren 1, M Schalling 1, I Johansson 1
PMCID: PMC52853  PMID: 1946468

Abstract

SH-SY5Y neuroblastoma cells undergo neuronal differentiation and their proliferation is inhibited when they are treated with phorbol 12-myristate 13-acetate (PMA). Insulin and insulin-like growth factor I (IGF-I) are mitogens for the nontreated SH-SY5Y cells, whereas the proliferative response to such factor stimulation is lost upon differentiation, in spite of the fact that the receptors for insulin and IGF-I remain expressed and functional in the differentiated cells. Here we show that the PMA-induced differentiation of SH-SY5Y cells grown in a serum-free medium is strongly potentiated by nanomolar concentrations of IGF-I, as judged by morphology and markers for neuronal differentiation--e.g., neuropeptide tyrosine and growth-associated protein 43. Also, insulin and IGF-II potentiated the phorbol ester-induced differentiation, although less efficiently than IGF-I. Using blocking anti-receptor antibodies, it could be shown that the differentiation induced by these factors, in combination with PMA, was primarily mediated through the IGF-I receptor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adashi E. Y., Resnick C. E., D'Ercole A. J., Svoboda M. E., Van Wyk J. J. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Rev. 1985 Summer;6(3):400–420. doi: 10.1210/edrv-6-3-400. [DOI] [PubMed] [Google Scholar]
  2. Adem A., Mattsson M. E., Nordberg A., Påhlman S. Muscarinic receptors in human SH-SY5Y neuroblastoma cell line: regulation by phorbol ester and retinoic acid-induced differentiation. Brain Res. 1987 Jun;430(2):235–242. doi: 10.1016/0165-3806(87)90156-8. [DOI] [PubMed] [Google Scholar]
  3. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  4. Baskin D. G., Figlewicz D. P., Woods S. C., Porte D., Jr, Dorsa D. M. Insulin in the brain. Annu Rev Physiol. 1987;49:335–347. doi: 10.1146/annurev.ph.49.030187.002003. [DOI] [PubMed] [Google Scholar]
  5. Baskin D. G., Wilcox B. J., Figlewicz D. P., Dorsa D. M. Insulin and insulin-like growth factors in the CNS. Trends Neurosci. 1988 Mar;11(3):107–111. doi: 10.1016/0166-2236(88)90155-5. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Bjelfman C., Meyerson G., Cartwright C. A., Mellström K., Hammerling U., Påhlman S. Early activation of endogenous pp60src kinase activity during neuronal differentiation of cultured human neuroblastoma cells. Mol Cell Biol. 1990 Jan;10(1):361–370. doi: 10.1128/mcb.10.1.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blackwell T. K., Kretzner L., Blackwood E. M., Eisenman R. N., Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990 Nov 23;250(4984):1149–1151. doi: 10.1126/science.2251503. [DOI] [PubMed] [Google Scholar]
  9. Burgess S. K., Jacobs S., Cuatrecasas P., Sahyoun N. Characterization of a neuronal subtype of insulin-like growth factor I receptor. J Biol Chem. 1987 Feb 5;262(4):1618–1622. [PubMed] [Google Scholar]
  10. Cattaneo E., McKay R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature. 1990 Oct 25;347(6295):762–765. doi: 10.1038/347762a0. [DOI] [PubMed] [Google Scholar]
  11. Collum R. G., Alt F. W. Are myc proteins transcription factors? Cancer Cells. 1990 Mar;2(3):69–75. [PubMed] [Google Scholar]
  12. Demarquay D., Dumontier M. F., Tsagris L., Bourguignon J., Nataf V., Corvol M. T. In vitro insulin-like growth factor I interaction with cartilage cells derived from postnatal animals. Horm Res. 1990;33(2-4):111–115. doi: 10.1159/000181493. [DOI] [PubMed] [Google Scholar]
  13. DiCicco-Bloom E., Black I. B. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4066–4070. doi: 10.1073/pnas.85.11.4066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fried G., Lundberg J. M., Theodorsson-Norheim E. Subcellular storage and axonal transport of neuropeptide Y (NPY) in relation to catecholamines in the cat. Acta Physiol Scand. 1985 Sep;125(1):145–154. doi: 10.1111/j.1748-1716.1985.tb07701.x. [DOI] [PubMed] [Google Scholar]
  15. Gammeltoft S., Ballotti R., Nielsen F. C., Kowalski A., Van Obberghen E. Receptors for insulin-like growth factors in the central nervous system: structure and function. Horm Metab Res. 1988 Jul;20(7):436–442. doi: 10.1055/s-2007-1010854. [DOI] [PubMed] [Google Scholar]
  16. Garofalo R. S., Rosen O. M. Insulin and insulinlike growth factor 1 (IGF-1) receptors during central nervous system development: expression of two immunologically distinct IGF-1 receptor beta subunits. Mol Cell Biol. 1989 Jul;9(7):2806–2817. doi: 10.1128/mcb.9.7.2806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goslin K., Schreyer D. J., Skene J. H., Banker G. Development of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones. Nature. 1988 Dec 15;336(6200):672–674. doi: 10.1038/336672a0. [DOI] [PubMed] [Google Scholar]
  18. Hammerling U., Bjelfman C., Påhlman S. Different regulation of N- and c-myc expression during phorbol ester-induced maturation of human SH-SY5Y neuroblastoma cells. Oncogene. 1987;2(1):73–77. [PubMed] [Google Scholar]
  19. Lundberg J. M., Terenius L., Hökfelt T., Martling C. R., Tatemoto K., Mutt V., Polak J., Bloom S., Goldstein M. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand. 1982 Dec;116(4):477–480. doi: 10.1111/j.1748-1716.1982.tb07171.x. [DOI] [PubMed] [Google Scholar]
  20. Mattsson M. E., Enberg G., Ruusala A. I., Hall K., Påhlman S. Mitogenic response of human SH-SY5Y neuroblastoma cells to insulin-like growth factor I and II is dependent on the stage of differentiation. J Cell Biol. 1986 May;102(5):1949–1954. doi: 10.1083/jcb.102.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mattsson M. E., Hammerling U., Mohall E., Hall K., Påhlman S. Mitogenically uncoupled insulin and IGF-I receptors of differentiated human neuroblastoma cells are functional and mediate ligand-induced signals. Growth Factors. 1990;2(4):251–265. doi: 10.3109/08977199009167020. [DOI] [PubMed] [Google Scholar]
  22. McQuillan D. J., Handley C. J., Campbell M. A., Bolis S., Milway V. E., Herington A. C. Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage. Biochem J. 1986 Dec 1;240(2):423–430. doi: 10.1042/bj2400423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Påhlman S., Mamaeva S., Meyerson G., Mattsson M. E., Bjelfman C., Ortoft E., Hammerling U. Human neuroblastoma cells in culture: a model for neuronal cell differentiation and function. Acta Physiol Scand Suppl. 1990;592:25–37. [PubMed] [Google Scholar]
  24. Påhlman S., Odelstad L., Larsson E., Grotte G., Nilsson K. Phenotypic changes of human neuroblastoma cells in culture induced by 12-O-tetradecanoyl-phorbol-13-acetate. Int J Cancer. 1981 Nov 15;28(5):583–589. doi: 10.1002/ijc.2910280509. [DOI] [PubMed] [Google Scholar]
  25. Påhlman S., Ruusala A. I., Abrahamsson L., Odelstad L., Nilsson K. Kinetics and concentration effects of TPA-induced differentiation of cultured human neuroblastoma cells. Cell Differ. 1983 Mar;12(3):165–170. doi: 10.1016/0045-6039(83)90006-4. [DOI] [PubMed] [Google Scholar]
  26. Recio-Pinto E., Ishii D. N. Insulin and insulinlike growth factor receptors regulating neurite formation in cultured human neuroblastoma cells. J Neurosci Res. 1988 Mar;19(3):312–320. doi: 10.1002/jnr.490190306. [DOI] [PubMed] [Google Scholar]
  27. Recio-Pinto E., Lang F. F., Ishii D. N. Insulin and insulin-like growth factor II permit nerve growth factor binding and the neurite formation response in cultured human neuroblastoma cells. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2562–2566. doi: 10.1073/pnas.81.8.2562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Recio-Pinto E., Rechler M. M., Ishii D. N. Effects of insulin, insulin-like growth factor-II, and nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons. J Neurosci. 1986 May;6(5):1211–1219. doi: 10.1523/JNEUROSCI.06-05-01211.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Roger L. J., Fellows R. E. Stimulation of ornithine decarboxylase activity by insulin in developing rat brain. Endocrinology. 1980 Feb;106(2):619–625. doi: 10.1210/endo-106-2-619. [DOI] [PubMed] [Google Scholar]
  30. Schalling M., Dagerlind A., Brené S., Hallman H., Djurfeldt M., Persson H., Terenius L., Goldstein M., Schlesinger D., Hökfelt T. Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8306–8310. doi: 10.1073/pnas.85.21.8306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  32. Scott I. G., Akerman K. E., Heikkilä J. E., Kaila K., Andersson L. C. Development of a neural phenotype in differentiating ganglion cell-derived human neuroblastoma cells. J Cell Physiol. 1986 Aug;128(2):285–292. doi: 10.1002/jcp.1041280221. [DOI] [PubMed] [Google Scholar]
  33. Shemer J., Raizada M. K., Masters B. A., Ota A., LeRoith D. Insulin-like growth factor I receptors in neuronal and glial cells. Characterization and biological effects in primary culture. J Biol Chem. 1987 Jun 5;262(16):7693–7699. [PubMed] [Google Scholar]
  34. Sporn M. B., Roberts A. B. Peptide growth factors are multifunctional. Nature. 1988 Mar 17;332(6161):217–219. doi: 10.1038/332217a0. [DOI] [PubMed] [Google Scholar]
  35. Weiler R., Meyerson G., Fischer-Colbrie R., Laslop A., Påhlman S., Floor E., Winkler H. Divergent changes of chromogranin A/secretogranin II levels in differentiating human neuroblastoma cells. FEBS Lett. 1990 Jun 4;265(1-2):27–29. doi: 10.1016/0014-5793(90)80875-j. [DOI] [PubMed] [Google Scholar]
  36. Xia X., Choi Y. S. Functional roles of gamma interferon in proliferation and differentiation of human B cell subpopulations. J Biol Response Mod. 1988 Jun;7(3):283–295. [PubMed] [Google Scholar]

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