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. 1982 Jan;79(2):456–460. doi: 10.1073/pnas.79.2.456

Purification and properties of a rat liver protein that specifically inhibits the proliferation of nonmalignant epithelial cells from rat liver.

J B McMahon, J G Farrelly, P T Iype
PMCID: PMC345762  PMID: 6952196

Abstract

An inhibitor of cell proliferation was purified from rat liver by alcohol precipitation, ultrafiltration, and DEAE-cellulose chromatography. The hepatic proliferation inhibitor was shown to be pure by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, analytical isoelectric focusing, and high-performance liquid chromatography. The hepatic proliferation inhibitor was found to have a molecular weight of 26,000 and an isoelectric point of 4.65. This protein inhibited the proliferation of nonmalignant rat liver cells in culture, and removal of the protein reversed the inhibition produced by low doses. It exerted no effect on the proliferation of malignant rat liver cells.

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Selected References

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

  1. Allen J. C. Damn the dogma. Nature. 1978 Dec 14;276(5689):669–669. doi: 10.1038/276669a0. [DOI] [PubMed] [Google Scholar]
  2. Barra R., Parsons J., Koch M. R., Lea M. A. Soluble factors from liver and hepatomas which inhibit [3H]thymidine incorporation into DNA of Novikoff hepatoma cells. Cancer Res. 1979 May;39(5):1655–1660. [PubMed] [Google Scholar]
  3. Bowen-Pope D. F., Vidair C., Sanui H., Rubin A. H. Separate roles for calcium and magnesium in their synergistic effect on uridine uptake by cultured cells: significance for growth control. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1308–1312. doi: 10.1073/pnas.76.3.1308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bullough W. S. Mitotic and functional homeostasis: a speculative review. Cancer Res. 1965 Nov;25(10):1683–1727. [PubMed] [Google Scholar]
  5. Davison P., Liu S., Karasek M. Limitations in the use of [3H]thymidine incorporation into DNA as an indicator of epidermal keratinocyte proliferation in vitro. Cell Tissue Kinet. 1979 Nov;12(6):605–614. doi: 10.1111/j.1365-2184.1979.tb00180.x. [DOI] [PubMed] [Google Scholar]
  6. Diezel W., Kopperschläger G., Hofmann E. An improved procedure for protein staining in polyacrylamide gels with a new type of Coomassie Brilliant Blue. Anal Biochem. 1972 Aug;48(2):617–620. doi: 10.1016/0003-2697(72)90117-0. [DOI] [PubMed] [Google Scholar]
  7. Fairbanks G., Steck T. L., Wallach D. F. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971 Jun 22;10(13):2606–2617. doi: 10.1021/bi00789a030. [DOI] [PubMed] [Google Scholar]
  8. Harrington W. N., Godman G. C. A selective inhibitor of cell proliferation from normal serum. Proc Natl Acad Sci U S A. 1980 Jan;77(1):423–427. doi: 10.1073/pnas.77.1.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holley R. W., Armour R., Baldwin J. H. Density-dependent regulation of growth of BSC-1 cells in cell culture: control of growth by low molecular weight nutrients. Proc Natl Acad Sci U S A. 1978 Jan;75(1):339–341. doi: 10.1073/pnas.75.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holley R. W., Böhlen P., Fava R., Baldwin J. H., Kleeman G., Armour R. Purification of kidney epithelial cell growth inhibitors. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5989–5992. doi: 10.1073/pnas.77.10.5989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Houck J. C., Hennings H. Chalones. Specific endogenous mitotic inhibitors. FEBS Lett. 1973 May 15;32(1):1–8. doi: 10.1016/0014-5793(73)80721-5. [DOI] [PubMed] [Google Scholar]
  12. Iype P. T., Allen T. D. Identification of transformed rat liver epithelial cells in culture. Cancer Lett. 1979 Jan;6(1):27–32. doi: 10.1016/s0304-3835(79)80016-6. [DOI] [PubMed] [Google Scholar]
  13. Iype P. T. Cultures from adult rat liver cells. I. Establishment of monolayer cell-cultures from normal liver. J Cell Physiol. 1971 Oct;78(2):281–288. doi: 10.1002/jcp.1040780217. [DOI] [PubMed] [Google Scholar]
  14. Iype P. T., McMahon J. B. Lack of correlation between the response to a proliferation inhibitor and other transformation markers in a mutant liver cell line. Cancer Res. 1981 Sep;41(9 Pt 1):3352–3354. [PubMed] [Google Scholar]
  15. Kuo C. Y., Yoo T. J. In vitro inhibition of tritiated thymidine uptake in Morris hepatoma cells by normal rat liver extract: a possible liver chalone. J Natl Cancer Inst. 1977 Dec;59(6):1691–1695. doi: 10.1093/jnci/59.6.1691. [DOI] [PubMed] [Google Scholar]
  16. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  17. Lipkin G., Rosenberg M., Knecht M. E. Factors affecting growth of normal and malignant cells in vitro. Biochem Pharmacol. 1976 Jun 15;25(12):1333–1337. doi: 10.1016/0006-2952(76)90100-3. [DOI] [PubMed] [Google Scholar]
  18. McMahon J. B., Iype P. T. Specific inhibition of proliferation of nonmalignant rat hepatic cells by a factor from rat liver. Cancer Res. 1980 Apr;40(4):1249–1254. [PubMed] [Google Scholar]
  19. Miyamoto M., Terayama H. Nature of rat liver cell sap factors inhibiting the DNA synthesis in tumour cells. Biochim Biophys Acta. 1971 Jan 28;228(2):324–330. doi: 10.1016/0005-2787(71)90040-2. [DOI] [PubMed] [Google Scholar]
  20. Molimard R., Pietu G., Chany E., Trincal G., Frayssinet An inhibitor of hepatoma cells multiplication in the efferent fluid from isolated perfused rat liver. Biomedicine. 1975 Dec 20;23(10):434–437. [PubMed] [Google Scholar]
  21. Nadal C. Control of liver growth by growth inhibitors (chalones). Arch Toxicol Suppl. 1979;(2):131–142. doi: 10.1007/978-3-642-67265-1_11. [DOI] [PubMed] [Google Scholar]
  22. Potter V. R. Initiation and promotion in cancer formation: the importance of studies on intercellular communication. Yale J Biol Med. 1980 Sep-Oct;53(5):367–384. [PMC free article] [PubMed] [Google Scholar]
  23. Potter V. R. The present status of the blocked ontogeny hypothesis of neoplasia: the thalassemia connection. Oncodev Biol Med. 1981;2(4):243–266. [PubMed] [Google Scholar]
  24. Sekas G., Cook R. T. The isolation of a low molecular weight inhibitor of [3H]TdR incorporation into hepatic DNA. Exp Cell Res. 1976 Oct 15;102(2):422–425. doi: 10.1016/0014-4827(76)90061-6. [DOI] [PubMed] [Google Scholar]
  25. Steck P. A., Voss P. G., Wang J. L. Growth control in cultured 3T3 fibroblasts. Assays of cell proliferation and demonstration of a growth inhibitory activity. J Cell Biol. 1979 Dec;83(3):562–575. doi: 10.1083/jcb.83.3.562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Verly W. G., Deschamps Y., Pushpathadam J., Desrosiers M. The hepatic chalone. I. Assay method for the hormone and purification of the rabbit liver chalone. Can J Biochem. 1971 Dec;49(12):1376–1383. doi: 10.1139/o71-198. [DOI] [PubMed] [Google Scholar]
  27. Vinet B., Verly W. G. Purification of a protein inhibitor of DNA synthesis in cells of hepatic origin. Eur J Cancer. 1976 Mar;12(3):211–218. doi: 10.1016/0014-2964(76)90244-9. [DOI] [PubMed] [Google Scholar]

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