Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Dec 1;111(6):2703–2711. doi: 10.1083/jcb.111.6.2703

The tissue-specific pathways regulating cell proliferation are inherited independently in somatic hybrid between thyroid and liver cells

PMCID: PMC2116429  PMID: 2177478

Abstract

Thyroid stimulating hormone (TSH) and insulin-like growth factors type 1 (IGF-I) regulate the proliferation and differentiation of cultured thyroid cells but not of cultured liver cells. We have examined the influence of TSH and IGF-I on the metabolic functions and proliferation of somatic hybrids obtained by fusing rat thyroid cells (FRTL5) with rat liver cells (BRL). While IGF-I is able to stimulate the proliferation of the hybrid cells (TxL) TSH fails to induce their growth. However, the hybrid TxL cells have surface TSH receptors with normal ligand characteristics. The addition of TSH to TxL cells led to typical enhancement of cAMP production and depolymerization of actin filaments. Yet, TSH failed to stimulate iodine uptake in the hybrid cells. Interestingly, iodine inhibited TxL proliferation induced by IGF- I but not by serum. It is concluded that the hybrid TxL cells inherited from the parental thyroid cells several important differentiated traits including mitogenic pathways induced and used by IGF-I, functional TSH receptors, and sensitivity to the inhibitory action of iodine.

Full Text

The Full Text of this article is available as a PDF (2.0 MB).

Selected References

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

  1. Ambesi-Impiombato F. S., Villone G. The FRTL-5 thyroid cell strain as a model for studies on thyroid cell growth. Acta Endocrinol Suppl (Copenh) 1987;281:242–245. doi: 10.1530/acta.0.114s242. [DOI] [PubMed] [Google Scholar]
  2. Bachrach L. K., Eggo M. C., Mak W. W., Burrow G. N. Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells. Endocrinology. 1985 Apr;116(4):1603–1609. doi: 10.1210/endo-116-4-1603. [DOI] [PubMed] [Google Scholar]
  3. Becks G. P., Eggo M. C., Burrow G. N. Organic iodine inhibits deoxyribonucleic acid synthesis and growth in FRTL-5 thyroid cells. Endocrinology. 1988 Jul;123(1):545–551. doi: 10.1210/endo-123-1-545. [DOI] [PubMed] [Google Scholar]
  4. Beguinot F., Kahn C. R., Moses A. C., Smith R. J. Distinct biologically active receptors for insulin, insulin-like growth factor I, and insulin-like growth factor II in cultured skeletal muscle cells. J Biol Chem. 1985 Dec 15;260(29):15892–15898. [PubMed] [Google Scholar]
  5. Brown A. L., Graham D. E., Nissley S. P., Hill D. J., Strain A. J., Rechler M. M. Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem. 1986 Oct 5;261(28):13144–13150. [PubMed] [Google Scholar]
  6. Chin A. C., Fournier R. E. A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1614–1618. doi: 10.1073/pnas.84.6.1614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clemmons D. R., Van Wyk J. J. Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J Clin Invest. 1985 Jun;75(6):1914–1918. doi: 10.1172/JCI111906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. D'Ercole A. J., Applewhite G. T., Underwood L. E. Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol. 1980 Mar 15;75(2):315–328. doi: 10.1016/0012-1606(80)90166-9. [DOI] [PubMed] [Google Scholar]
  9. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davidson R. L. Gene expression in somatic cell hybrids. Annu Rev Genet. 1974;8:195–218. doi: 10.1146/annurev.ge.08.120174.001211. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Errick J. E., Ing K. W., Eggo M. C., Burrow G. N. Growth and differentiation in cultured human thyroid cells: effects of epidermal growth factor and thyrotropin. In Vitro Cell Dev Biol. 1986 Jan;22(1):28–36. doi: 10.1007/BF02623438. [DOI] [PubMed] [Google Scholar]
  13. Fougère C., Weiss M. C. Phenotypic exclusion in mouse melanoma-rat hepatoma hybrid cells: pigment and albumin production are not reexpressed simultaneously. Cell. 1978 Nov;15(3):843–854. doi: 10.1016/0092-8674(78)90269-6. [DOI] [PubMed] [Google Scholar]
  14. Goldfine I. D., Amir S. M., Petersen A. W., Ingbar S. H. Preparation of biologically active 125I-TSH. Endocrinology. 1974 Nov;95(5):1228–1233. doi: 10.1210/endo-95-5-1228. [DOI] [PubMed] [Google Scholar]
  15. Gärtner R., Greil W., Demharter R., Horn K. Involvement of cyclic AMP, iodide and metabolites of arachidonic acid in the regulation of cell proliferation of isolated porcine thyroid follicles. Mol Cell Endocrinol. 1985 Sep;42(2):145–155. doi: 10.1016/0303-7207(85)90102-9. [DOI] [PubMed] [Google Scholar]
  16. Han V. K., D'Ercole A. J., Lund P. K. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science. 1987 Apr 10;236(4798):193–197. doi: 10.1126/science.3563497. [DOI] [PubMed] [Google Scholar]
  17. Ingbar S. H. Autoregulation of the thyroid. Response to iodide excess and depletion. Mayo Clin Proc. 1972 Nov;47(11):814–823. [PubMed] [Google Scholar]
  18. Jin S., Hornicek F. J., Neylan D., Zakarija M., McKenzie J. M. Evidence that adenosine 3',5'-monophosphate mediates stimulation of thyroid growth in FRTL5 cells. Endocrinology. 1986 Aug;119(2):802–810. doi: 10.1210/endo-119-2-802. [DOI] [PubMed] [Google Scholar]
  19. Killary A. M., Fournier R. E. A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell. 1984 Sep;38(2):523–534. doi: 10.1016/0092-8674(84)90507-5. [DOI] [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. Lichtsteiner S., Wuarin J., Schibler U. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene. Cell. 1987 Dec 24;51(6):963–973. doi: 10.1016/0092-8674(87)90583-6. [DOI] [PubMed] [Google Scholar]
  22. Lombardi A., Veneziani B. M., Tramontano D., Ingbar S. H. Independent and interactive effects of tetradecanoyl phorbol acetate on growth and differentiated functions of FRTL5 cells. Endocrinology. 1988 Sep;123(3):1544–1552. doi: 10.1210/endo-123-3-1544. [DOI] [PubMed] [Google Scholar]
  23. Maciel R. M., Moses A. C., Villone G., Tramontano D., Ingbar S. H. Demonstration of the production and physiological role of insulin-like growth factor II in rat thyroid follicular cells in culture. J Clin Invest. 1988 Nov;82(5):1546–1553. doi: 10.1172/JCI113764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nissley S. P., Short P. A., Rechler M. M., Podskalny J. M., Coon H. G. Proliferation of Buffalo rat liver cells in serum-free medium does not depend upon multiplication-stimulating activity (MSA). Cell. 1977 Jun;11(2):441–446. doi: 10.1016/0092-8674(77)90062-9. [DOI] [PubMed] [Google Scholar]
  25. Pilistine S. J., Moses A. C., Munro H. N. Insulin-like growth factor receptors in rat placental membranes. Endocrinology. 1984 Sep;115(3):1060–1065. doi: 10.1210/endo-115-3-1060. [DOI] [PubMed] [Google Scholar]
  26. Roger P. P., Dumont J. E. Epidermal growth factor controls the proliferation and the expression of differentiation in canine thyroid cells in primary culture. FEBS Lett. 1982 Aug 2;144(2):209–212. doi: 10.1016/0014-5793(82)80639-x. [DOI] [PubMed] [Google Scholar]
  27. Roger P. P., Dumont J. E. Thyrotropin is a potent growth factor for normal human thyroid cells in primary culture. Biochem Biophys Res Commun. 1987 Dec 16;149(2):707–711. doi: 10.1016/0006-291x(87)90425-6. [DOI] [PubMed] [Google Scholar]
  28. Roger P. P., Servais P., Dumont J. E. Stimulation by thyrotropin and cyclic AMP of the proliferation of quiescent canine thyroid cells cultured in a defined medium containing insulin. FEBS Lett. 1983 Jul 4;157(2):323–329. doi: 10.1016/0014-5793(83)80569-9. [DOI] [PubMed] [Google Scholar]
  29. Roger P., Taton M., Van Sande J., Dumont J. E. Mitogenic effects of thyrotropin and adenosine 3',5'-monophosphate in differentiated normal human thyroid cells in vitro. J Clin Endocrinol Metab. 1988 Jun;66(6):1158–1165. doi: 10.1210/jcem-66-6-1158. [DOI] [PubMed] [Google Scholar]
  30. Smith P., Wynford-Thomas D., Stringer B. M., Williams E. D. Growth factor control of rat thyroid follicular cell proliferation. Endocrinology. 1986 Oct;119(4):1439–1445. doi: 10.1210/endo-119-4-1439. [DOI] [PubMed] [Google Scholar]
  31. Stiles A. D., Sosenko I. R., D'Ercole A. J., Smith B. T. Relation of kidney tissue somatomedin-C/insulin-like growth factor I to postnephrectomy renal growth in the rat. Endocrinology. 1985 Dec;117(6):2397–2401. doi: 10.1210/endo-117-6-2397. [DOI] [PubMed] [Google Scholar]
  32. Tramontano D., Avivi A., Ambesi-Impiombato F. S., Barak L., Geiger B., Schlessinger J. Thyrotropin induces changes in the morphology and the organization of microfilament structures in cultured thyroid cells. Exp Cell Res. 1982 Feb;137(2):269–275. doi: 10.1016/0014-4827(82)90027-1. [DOI] [PubMed] [Google Scholar]
  33. Tramontano D., Chin W. W., Moses A. C., Ingbar S. H. Thyrotropin and dibutyryl cyclic AMP increase levels of c-myc and c-fos mRNAs in cultured rat thyroid cells. J Biol Chem. 1986 Mar 25;261(9):3919–3922. [PubMed] [Google Scholar]
  34. Tramontano D., Cushing G. W., Moses A. C., Ingbar S. H. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves'-IgG. Endocrinology. 1986 Aug;119(2):940–942. doi: 10.1210/endo-119-2-940. [DOI] [PubMed] [Google Scholar]
  35. Tramontano D., Ingbar S. H. Properties and regulation of the thyrotropin receptor in the FRTL5 rat thyroid cell line. Endocrinology. 1986 May;118(5):1945–1951. doi: 10.1210/endo-118-5-1945. [DOI] [PubMed] [Google Scholar]
  36. Tramontano D., Moses A. C., Picone R., Ingbar S. H. Characterization and regulations of the receptor for insulin-like growth factor-I in the FRTL-5 rat thyroid follicular cell line. Endocrinology. 1987 Feb;120(2):785–790. doi: 10.1210/endo-120-2-785. [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. Tramontano D., Veneziani B. M., Lombardi A., Villone G., Ingbar S. H. Iodine inhibits the proliferation of rat thyroid cells in culture. Endocrinology. 1989 Aug;125(2):984–992. doi: 10.1210/endo-125-2-984. [DOI] [PubMed] [Google Scholar]
  39. Westermark B., Portor K. R. Hormonally induced changes in the cytoskeleton of human thyroid cells in culture. J Cell Biol. 1982 Jul;94(1):42–50. doi: 10.1083/jcb.94.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Westermark K., Karlsson F. A., Westermark B. Epidermal growth factor modulates thyroid growth and function in culture. Endocrinology. 1983 May;112(5):1680–1686. doi: 10.1210/endo-112-5-1680. [DOI] [PubMed] [Google Scholar]
  41. Westermark K., Westermark B. Mitogenic effect of epidermal growth factor on sheep thyroid cells in culture. Exp Cell Res. 1982 Mar;138(1):47–55. doi: 10.1016/0014-4827(82)90089-1. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES