Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Nov;86(5):1548–1555. doi: 10.1172/JCI114874

Relationship between proliferation and cell cycle-dependent Ca2+ influx induced by a combination of thyrotropin and insulin-like growth factor-I in rat thyroid cells.

K Takada 1, N Amino 1, H Tada 1, K Miyai 1
PMCID: PMC296902  PMID: 1700796

Abstract

The mechanism of cell proliferation by a combination of thyroid-stimulating hormone (TSH) and insulin-like growth factor-I (IGF-I) was studied in rat thyroid (FRTL-5) cells. IGF-I stimulated an approximately 3.5-fold increase in the rate of Ca2+ influx sustained for at least 6 h in TSH-pretreated cells but not in quiescent cells. The significant cell proliferation was observed when TSH-primed cells were incubated with IGF-I for 24 h but not for 12 h. IGF-I stimulated the rate of Ca2+ influx in a dose-dependent manner that was similar to that for induction of DNA synthesis. Both Ca2+ influx and DNA synthesis observed in response to IGF-I in TSH-primed cells were inhibited by cobalt. In addition, the stimulations of Ca2+ influx and DNA synthesis by IGF-I were dependent on extracellular Ca2+ in TSH-pretreated cells. When TSH-primed cells were pretreated with pertussis toxin, both IGF-I-induced Ca2+ influx and DNA synthesis were abolished. However, pertussis toxin did not block the priming action of TSH or forskolin. When calcium entry was induced by Bay K8644, it stimulated cell growth in TSH-primed cells but not in quiescent cells. Moreover, cobalt and lanthanum inhibited DNA synthesis even when added several hours after the addition of Bay K8644 but not when added 24 h after the growth factor in TSH-primed cells. These findings suggest that at least two important mechanisms may work in response to IGF-I only in the TSH-primed G1 phase of the cell cycle: first, IGF-I can activate directly or indirectly the Ca2+ channel via a pertussis toxin-sensitive substrate in TSH-primed cells; and second, a long lasting calcium entry by IGF-I may be a cell cycle-dependent mitogenic signal.

Full text

PDF
1548

Selected References

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

  1. Ambesi-Impiombato F. S., Parks L. A., Coon H. G. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3455–3459. doi: 10.1073/pnas.77.6.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  3. Betsholtz C., Westermark B. Growth factor-induced proliferation of human fibroblasts in serum-free culture depends on cell density and extracellular calcium concentration. J Cell Physiol. 1984 Feb;118(2):203–210. doi: 10.1002/jcp.1041180213. [DOI] [PubMed] [Google Scholar]
  4. Brenner-Gati L., Berg K. A., Gershengorn M. C. Thyroid-stimulating hormone and insulin-like growth factor-1 synergize to elevate 1,2-diacylglycerol in rat thyroid cells. Stimulation of DNA synthesis via interaction between lipid and adenylyl cyclase signal transduction systems. J Clin Invest. 1988 Sep;82(3):1144–1148. doi: 10.1172/JCI113672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Church J. G., Buick R. N. G-protein-mediated epidermal growth factor signal transduction in a human breast cancer cell line. Evidence for two intracellular pathways distinguishable by pertussis toxin. J Biol Chem. 1988 Mar 25;263(9):4242–4246. [PubMed] [Google Scholar]
  6. Colletta G., Cirafici A. M., Vecchio G. Induction of the c-fos oncogene by thyrotropic hormone in rat thyroid cells in culture. Science. 1986 Jul 25;233(4762):458–460. doi: 10.1126/science.3726540. [DOI] [PubMed] [Google Scholar]
  7. Corda D., Marcocci C., Kohn L. D., Axelrod J., Luini A. Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of alpha 1-adrenergic receptors in cultured rat thyroid cells. J Biol Chem. 1985 Aug 5;260(16):9230–9236. [PubMed] [Google Scholar]
  8. Damante G., Cox F., Rapoport B. IGF-I increases c-fos expression in FRTL5 rat thyroid cells by activating the c-fos promoter. Biochem Biophys Res Commun. 1988 Mar 30;151(3):1194–1199. doi: 10.1016/s0006-291x(88)80492-3. [DOI] [PubMed] [Google Scholar]
  9. Dere W. H., Hirayu H., Rapoport B. TSH and cAMP enhance expression of the myc proto-oncogene in cultured thyroid cells. Endocrinology. 1985 Nov;117(5):2249–2251. doi: 10.1210/endo-117-5-2249. [DOI] [PubMed] [Google Scholar]
  10. Dere W. H., Rapoport B. Control of growth in cultured rat thyroid cells. Mol Cell Endocrinol. 1986 Mar;44(3):195–199. doi: 10.1016/0303-7207(86)90124-3. [DOI] [PubMed] [Google Scholar]
  11. Farese R. V., Nair G. P., Standaert M. L., Cooper D. R. Epidermal growth factor and insulin-like growth factor I stimulate the hydrolysis of the insulin-sensitive phosphatidylinositol-glycan in BC3H-1 myocytes. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1346–1352. doi: 10.1016/s0006-291x(88)80780-0. [DOI] [PubMed] [Google Scholar]
  12. Field J. B., Ealey P. A., Marshall N. J., Cockcroft S. Thyroid-stimulating hormone stimulates increases in inositol phosphates as well as cyclic AMP in the FRTL-5 rat thyroid cell line. Biochem J. 1987 Nov 1;247(3):519–524. doi: 10.1042/bj2470519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goligorsky M. S., Menton D. N., Laszlo A., Lum H. Nature of thrombin-induced sustained increase in cytosolic calcium concentration in cultured endothelial cells. J Biol Chem. 1989 Oct 5;264(28):16771–16775. [PubMed] [Google Scholar]
  14. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  15. Hazelton B., Mitchell B., Tupper J. Calcium, magnesium, and growth control in the WI-38 human fibroblast cell. J Cell Biol. 1979 Nov;83(2 Pt 1):487–498. doi: 10.1083/jcb.83.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Holt J. T., Gopal T. V., Moulton A. D., Nienhuis A. W. Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4794–4798. doi: 10.1073/pnas.83.13.4794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Izant J. G. The role of calcium ions during mitosis. Calcium participates in the anaphase trigger. Chromosoma. 1983;88(1):1–10. doi: 10.1007/BF00329497. [DOI] [PubMed] [Google Scholar]
  18. Kaczmarek L., Hyland J. K., Watt R., Rosenberg M., Baserga R. Microinjected c-myc as a competence factor. Science. 1985 Jun 14;228(4705):1313–1315. doi: 10.1126/science.4001943. [DOI] [PubMed] [Google Scholar]
  19. Laurent E., Mockel J., Van Sande J., Graff I., Dumont J. E. Dual activation by thyrotropin of the phospholipase C and cyclic AMP cascades in human thyroid. Mol Cell Endocrinol. 1987 Aug;52(3):273–278. doi: 10.1016/0303-7207(87)90055-4. [DOI] [PubMed] [Google Scholar]
  20. Leof E. B., Wharton W., van Wyk J. J., Pledger W. J. Epidermal growth factor (EGF) and somatomedin C regulate G1 progression in competent BALB/c-3T3 cells. Exp Cell Res. 1982 Sep;141(1):107–115. doi: 10.1016/0014-4827(82)90073-8. [DOI] [PubMed] [Google Scholar]
  21. Low M. G., Saltiel A. R. Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science. 1988 Jan 15;239(4837):268–275. doi: 10.1126/science.3276003. [DOI] [PubMed] [Google Scholar]
  22. Luttrell L. M., Hewlett E. L., Romero G., Rogol A. D. Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes. J Biol Chem. 1988 May 5;263(13):6134–6141. [PubMed] [Google Scholar]
  23. Mauger J. P., Poggioli J., Guesdon F., Claret M. Noradrenaline, vasopressin and angiotensin increase Ca2+ influx by opening a common pool of Ca2+ channels in isolated rat liver cells. Biochem J. 1984 Jul 1;221(1):121–127. doi: 10.1042/bj2210121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Muldoon L. L., Rodland K. D., Magun B. E. Transforming growth factor beta and epidermal growth factor alter calcium influx and phosphatidylinositol turnover in rat-1 fibroblasts. J Biol Chem. 1988 Dec 15;263(35):18834–18841. [PubMed] [Google Scholar]
  25. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  26. Okajima F., Sho K., Kondo Y. Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptor-mediated iodide efflux and phosphoinositide turnover in FRTL-5 cells. Endocrinology. 1988 Aug;123(2):1035–1043. doi: 10.1210/endo-123-2-1035. [DOI] [PubMed] [Google Scholar]
  27. Pardee A. B. Molecules involved in proliferation of normal and cancer cells: presidential address. Cancer Res. 1987 Mar 15;47(6):1488–1491. [PubMed] [Google Scholar]
  28. Pledger W. J., Stiles C. D., Antoniades H. N., Scher C. D. Induction of DNA synthesis in BALB/c 3T3 cells by serum components: reevaluation of the commitment process. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481–4485. doi: 10.1073/pnas.74.10.4481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rasmussen C. D., Means A. R. Calmodulin is involved in regulation of cell proliferation. EMBO J. 1987 Dec 20;6(13):3961–3968. doi: 10.1002/j.1460-2075.1987.tb02738.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rasmussen C. D., Means A. R. Calmodulin is required for cell-cycle progression during G1 and mitosis. EMBO J. 1989 Jan;8(1):73–82. doi: 10.1002/j.1460-2075.1989.tb03350.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rubin J. B., Shia M. A., Pilch P. F. Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I. 1983 Sep 29-Oct 5Nature. 305(5933):438–440. doi: 10.1038/305438a0. [DOI] [PubMed] [Google Scholar]
  32. Sheela Rani C. S., Boyd A. E., 3rd, Field J. B. Effects of acetylcholine, TSH and other stimulators on intracellular calcium concentration in dog thyroid cells. Biochem Biophys Res Commun. 1985 Sep 30;131(3):1041–1047. doi: 10.1016/0006-291x(85)90195-0. [DOI] [PubMed] [Google Scholar]
  33. Stiles C. D., Capone G. T., Scher C. D., Antoniades H. N., Van Wyk J. J., Pledger W. J. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279–1283. doi: 10.1073/pnas.76.3.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Takada K., Amino N., Tetsumoto T., Miyai K. Phorbol esters have a dual action through protein kinase C in regulation of proliferation of FRTL-5 cells. FEBS Lett. 1988 Jul 4;234(1):13–16. doi: 10.1016/0014-5793(88)81292-4. [DOI] [PubMed] [Google Scholar]
  35. Takasu N., Handa Y., Shimizu Y., Yamada T. TSH-stimulated electrical excitation in thyroid cells. Biochem Biophys Res Commun. 1985 May 31;129(1):275–279. doi: 10.1016/0006-291x(85)91433-0. [DOI] [PubMed] [Google Scholar]
  36. Takasu N., Murakami M., Nagasawa Y., Yamada T., Shimizu Y., Kojima I., Ogata E. BAY-K-8644, a calcium channel agonist, induces a rise in cytoplasmic free calcium and iodide discharge in thyroid cells. Biochem Biophys Res Commun. 1987 Mar 30;143(3):1107–1111. doi: 10.1016/0006-291x(87)90366-4. [DOI] [PubMed] [Google Scholar]
  37. Tramontano D., Moses A. C., Veneziani B. M., Ingbar S. H. Adenosine 3',5'-monophosphate mediates both the mitogenic effect of thyrotropin and its ability to amplify the response to insulin-like growth factor I in FRTL5 cells. Endocrinology. 1988 Jan;122(1):127–132. doi: 10.1210/endo-122-1-127. [DOI] [PubMed] [Google Scholar]
  38. Truett A. P., 3rd, Verghese M. W., Dillon S. B., Snyderman R. Calcium influx stimulates a second pathway for sustained diacylglycerol production in leukocytes activated by chemoattractants. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1549–1553. doi: 10.1073/pnas.85.5.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ullrich A., Gray A., Tam A. W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Le Bon T., Kathuria S., Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. doi: 10.1002/j.1460-2075.1986.tb04528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES