Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1979 Mar 15;178(3):559–568. doi: 10.1042/bj1780559

Establishment of rat pancreatic endocrine cell lines by infection with simian virus 40.

E J Niesor, C B Wollheim, D H Mintz, B Blondel, A E Renold, R Weil
PMCID: PMC1186554  PMID: 222255

Abstract

The feasibility of infection and transformation by SV40 (simian virus 40) of primary cell cultures derived from newborn-rat pancreas was investigated. As judged by the presence of intranuclear SV40 T-antigen, exposure to the virus resulted specifically in infection and transformation of epithelioid (predominantly endocrine) cells. The transformed cells were subcultured (more than 64 passages) and cloned. Culture medium and acid/ethanol extracts of the cells did not contain detectable amounts of immunoreactive insulin after the third subculture. However, inoculation of such SV40-transformed pancreatic cells into immunodeficient rats results in tumours in which insulin production was partially restored through the passage in vivo, since the tumour cells contained and synthesized small amounts of immunoreactive insulin which co-migrated with an insulin marker on gel chromatography. Interestingly, the transformed cells maintained under tissue-culture conditions produced a protein immunologically related to insulin, soluble in aqueous buffer but insoluble in acid/ethanol. This 3000-dalton protein is too large to be a translation product of the rat preproinsulin 9S mRNA. SV40-transformed pancreatic cells might prove useful in the investigation of the factors controlling and maintaining insulin biosynthesis.

Full text

PDF
559

Images in this article

561Fig. 1.
on p.561

Selected References

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

  1. Adcock K., Austin M., Duckworth W. C., Solomon S. S., Murrell L. R. Human islet cell adenoma: metabolic analysis of the patient and of tumor cells in monolayer culture. Diabetologia. 1975 Dec;11(6):527–534. doi: 10.1007/BF01222102. [DOI] [PubMed] [Google Scholar]
  2. BUONASSISI V., SATO G., COHEN A. I. Hormone-producing cultures of adrenal and pituitary tumor origin. Proc Natl Acad Sci U S A. 1962 Jul 15;48:1184–1190. doi: 10.1073/pnas.48.7.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berget S. M., Moore C., Sharp P. A. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3171–3175. doi: 10.1073/pnas.74.8.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braaten J. T., Lee M. J., Schenk A., Mintz D. H. Removal of fibroblastoid cells from primary monolayer cultures of rat neonatal endocrine pancreas by sodium ethylmercurithiosalicylate. Biochem Biophys Res Commun. 1974 Nov 27;61(2):476–482. doi: 10.1016/0006-291x(74)90981-4. [DOI] [PubMed] [Google Scholar]
  5. Chan S. J., Keim P., Steiner D. F. Cell-free synthesis of rat preproinsulins: characterization and partial amino acid sequence determination. Proc Natl Acad Sci U S A. 1976 Jun;73(6):1964–1968. doi: 10.1073/pnas.73.6.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chick W. L. Beta cell replication in rat pancreatic monolayer cultures. Effects of glucose, tolbutamide, glucocorticoid, growth hormone and glucagon. Diabetes. 1973 Sep;22(9):687–693. doi: 10.2337/diab.22.9.687. [DOI] [PubMed] [Google Scholar]
  7. Chick W. L., Lauris V., Soeldner J. S., Tan M. H., Grinbergs M. Monolayer culture of a human pancreatic beta-cell adenoma. Metabolism. 1973 Sep;22(9):1217–1224. doi: 10.1016/0026-0495(73)90209-6. [DOI] [PubMed] [Google Scholar]
  8. Chick W. L., Like A. A., Lauris V. Pancreatic beta cell culture: preparation of purified monolayers. Endocrinology. 1975 Mar;96(3):637–643. doi: 10.1210/endo-96-3-637. [DOI] [PubMed] [Google Scholar]
  9. Chick W. L., Warren S., Chute R. N., Like A. A., Lauris V., Kitchen K. C. A transplantable insulinoma in the rat. Proc Natl Acad Sci U S A. 1977 Feb;74(2):628–632. doi: 10.1073/pnas.74.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DULBECCO R., FREEMAN G. Plaque production by the polyoma virus. Virology. 1959 Jul;8(3):396–397. doi: 10.1016/0042-6822(59)90043-1. [DOI] [PubMed] [Google Scholar]
  11. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. De Vitry F., Camier M., Czernichow P., Benda P., Cohen P., Tixier-Vidal A. Establishment of a clone of mouse hypothalamic neurosecretory cells synthesizing neurophysin and vasopressin. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3575–3579. doi: 10.1073/pnas.71.9.3575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. De Vitry F. Growth and differentiation of a primitive nervous cell line after in vivo transplantation into syngeneic mice. Nature. 1977 May 5;267(5606):48–50. doi: 10.1038/267048a0. [DOI] [PubMed] [Google Scholar]
  14. Defendi V. Transformation in vitro of mammalian cells by polyoma and Simian 40 viruses. Prog Exp Tumor Res. 1966;8:125–188. doi: 10.1159/000386007. [DOI] [PubMed] [Google Scholar]
  15. Deftos L. J., Rabson A. S., Buckle R. M., Aurbach G. D., Potts J. T., Jr Parathyroid hormone production in vitro by human parathyroid cells transformed by Simian virus 40. Science. 1968 Jan 26;159(3813):435–436. doi: 10.1126/science.159.3813.435. [DOI] [PubMed] [Google Scholar]
  16. Duguid J. R., Steiner D. F., Chick W. L. Partial purification and characterization of the mRNA for rat preproinsulin. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3539–3543. doi: 10.1073/pnas.73.10.3539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grimley P. M., Deftos L. J., Weeks J. R., Rabson A. S. Growth in vitro and ultrastructure of cells from a medullary carcinoma of the human thyroid gland: transformation by simian virus 40 and evidenc of thyrocalcitonin and prostaglandins. J Natl Cancer Inst. 1969 Apr;42(4):663–680. [PubMed] [Google Scholar]
  18. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  19. Lambert A. E., Blondel B., Kanazawa Y., Orci L., Renold A. E. Monolayer cell culture of neonatal rat pancreas: light microscopy and evidence for immunoreactive insulin synthesis and release. Endocrinology. 1972 Jan;90(1):239–248. doi: 10.1210/endo-90-1-239. [DOI] [PubMed] [Google Scholar]
  20. May E., May P., Weil R. Analysis of the events leading to SV40-induced chromosome replication and mitosis in primary mouse kidney cell cultures. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1208–1211. doi: 10.1073/pnas.68.6.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Steiner D. F., Clark J. L., Nolan C., Rubenstein A. H., Margoliash E., Aten B., Oyer P. E. Proinsulin and the biosynthesis of insulin. Recent Prog Horm Res. 1969;25:207–282. doi: 10.1016/b978-0-12-571125-8.50008-9. [DOI] [PubMed] [Google Scholar]
  22. Ullrich A., Shine J., Chirgwin J., Pictet R., Tischer E., Rutter W. J., Goodman H. M. Rat insulin genes: construction of plasmids containing the coding sequences. Science. 1977 Jun 17;196(4296):1313–1319. doi: 10.1126/science.325648. [DOI] [PubMed] [Google Scholar]
  23. Weil R. Viral 'tumor antigens': A novel type of mammalian regulator protein. Biochim Biophys Acta. 1978 Nov 17;516(3):301–388. doi: 10.1016/0304-419x(78)90012-4. [DOI] [PubMed] [Google Scholar]
  24. Wells S. A., Jr, Wurtman R. J., Rabson A. S. Viral neoplastic transformation of hamster pineal cells in vitro: retention of enzymatic function. Science. 1966 Oct 14;154(3746):278–279. doi: 10.1126/science.154.3746.278. [DOI] [PubMed] [Google Scholar]
  25. Yip C. C., Schimmer B. P. Human pancreatic islet tumor cells maintained in vitro. Diabetologia. 1973 Aug;9(4):251–254. doi: 10.1007/BF01221850. [DOI] [PubMed] [Google Scholar]
  26. de Haën C., Swanson E., Teller D. C. The evolutionary origin of proinsulin. Amino acid sequence homology with the trypsin-related serine proteases detected and evaluated by new statistical methods. J Mol Biol. 1976 Sep 25;106(3):639–661. doi: 10.1016/0022-2836(76)90256-4. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES