Skip to main content
Clinical Molecular Pathology logoLink to Clinical Molecular Pathology
. 1995 Jun;48(3):M153–M157. doi: 10.1136/mp.48.3.m153

Insulin-like growth factor II prevents apoptosis in a human teratoma derived cell line

M Granerus 1,2, P Bierke 1,2, W Zumkeller 1,2, J Smith 1,2, W Engström 1,2, P N Schofield 1,2
PMCID: PMC407949  PMID: 16695997

Abstract

Aim—To study how insulin-like growth factor II (IGF-II) affects the behaviour of human teratoma cells.

Methods—The human pluripotential teratoma cell line Tera 2 was cultured under serum-free conditions in the presence or absence of IGF-II. Effects on cell proliferation and apoptosis as well as on the expression of the proto-oncogene c-myc were studied.

Results—In this study we show that Tera 2 cells deprived of serum undergo programmed cell death (apoptosis). The onset of nuclear fragmentation was observed 12 hours after serum withdrawal. The morphological changes of the Tera 2 cell nuclei were confirmed by the occurrence of a nucleosome ladder. However, the constitutive expression of the proto-oncogene c-myc was not decreased in parallel with initiation of apoptosis. The apoptotic response to serum withdrawal could be counteracted by simultaneous addition of IGF-II. In addition it was found that human testicular tumours (seminoma and embryonal carcinoma) contain raised levels of insulin-like growth factors.

Conclusions—The precise roles of IGF-I and IGF-II have been unclear, and there is overwhelming evidence against these factors as primarily transforming agents. The finding that IGF-II apparently counteracts apoptosis in vitro may well explain its effects on tumours in vivo.

Keywords: Insulin-like growth factor

Keywords: teratoma cells

Keywords: testicular tumours

Keywords: apoptosis

Full text

PDF
M153

Images in this article

Selected References

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

  1. Biddle C., Li C. H., Schofield P. N., Tate V. E., Hopkins B., Engstrom W., Huskisson N. S., Graham C. F. Insulin-like growth factors and the multiplication of Tera-2, a human teratoma-derived cell line. J Cell Sci. 1988 Jul;90(Pt 3):475–484. doi: 10.1242/jcs.90.3.475. [DOI] [PubMed] [Google Scholar]
  2. Eastman A. Activation of programmed cell death by anticancer agents: cisplatin as a model system. Cancer Cells. 1990 Aug-Sep;2(8-9):275–280. [PubMed] [Google Scholar]
  3. Engström W., Hopkins B., Schofield P. Expression of growth regulatory genes in primary human testicular neoplasms. Int J Androl. 1987 Feb;10(1):79–84. doi: 10.1111/j.1365-2605.1987.tb00168.x. [DOI] [PubMed] [Google Scholar]
  4. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Harrington E. A., Bennett M. R., Fanidi A., Evan G. I. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 1994 Jul 15;13(14):3286–3295. doi: 10.1002/j.1460-2075.1994.tb06630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hyldahl L., Schofield P. N., Engström W. Stimulatory effects of basic fibroblast growth factor on DNA synthesis in the human embryonic cornea. Development. 1990 Jul;109(3):605–611. doi: 10.1242/dev.109.3.605. [DOI] [PubMed] [Google Scholar]
  8. Lennon S. V., Martin S. J., Cotter T. G. Induction of apoptosis (programmed cell death) in tumour cell lines by widely diverging stimuli. Biochem Soc Trans. 1990 Apr;18(2):343–345. doi: 10.1042/bst0180343. [DOI] [PubMed] [Google Scholar]
  9. Lin M., Jones R. C., Blackshaw A. W. The cycle of the seminiferous epithelium in the Japanese quail (Coturnix coturnix japonica) and estimation of its duration. J Reprod Fertil. 1990 Mar;88(2):481–490. doi: 10.1530/jrf.0.0880481. [DOI] [PubMed] [Google Scholar]
  10. Newsholme E. A. Glucose/fatty acid cycle: regulatory system. Nutrition. 1993 May-Jun;9(3):271–273. [PubMed] [Google Scholar]
  11. Pesce M., Farrace M. G., Piacentini M., Dolci S., De Felici M. Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis). Development. 1993 Aug;118(4):1089–1094. doi: 10.1242/dev.118.4.1089. [DOI] [PubMed] [Google Scholar]
  12. Prives C., Manfredi J. J. The p53 tumor suppressor protein: meeting review. Genes Dev. 1993 Apr;7(4):529–534. doi: 10.1101/gad.7.4.529. [DOI] [PubMed] [Google Scholar]
  13. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  14. Schofield P. N., Engstrom W., Lee A. J., Biddle C., Graham C. F. Expression of c-myc during differentiation of the human teratocarcinoma cell line Tera-2. J Cell Sci. 1987 Aug;88(Pt 1):57–64. doi: 10.1242/jcs.88.1.57. [DOI] [PubMed] [Google Scholar]
  15. Schofield P. N., Granerus M., Tally M., Engström W. The biological effects of a high molecular weight form of IGF II in a pluripotential human teratocarcinoma cell line. Anticancer Res. 1994 Mar-Apr;14(2A):533–538. [PubMed] [Google Scholar]
  16. Ward A., Bierke P., Pettersson E., Engström W. Insulin-like growth factors: growth, transgenes and imprinting. Zoolog Sci. 1994 Apr;11(2):167–174. [PubMed] [Google Scholar]
  17. Wyllie A. H. Apoptosis (the 1992 Frank Rose Memorial Lecture). Br J Cancer. 1993 Feb;67(2):205–208. doi: 10.1038/bjc.1993.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zhou B., Watts L. M., Hutson J. M. Germ cell development in neonatal mouse testes in vitro requires müllerian inhibiting substance. J Urol. 1993 Aug;150(2 Pt 2):613–616. doi: 10.1016/s0022-5347(17)35562-3. [DOI] [PubMed] [Google Scholar]

Articles from Clinical Molecular Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES