Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1971 Dec;68(12):3026–3030. doi: 10.1073/pnas.68.12.3026

Expression of Differentiated Functions in Hepatoma Cell Hybrids: Reappearance of Tyrosine Aminotransferase Inducibility after the Loss of Chromosomes*

Mary C Weiss 1, Michèle Chaplain 1
PMCID: PMC389583  PMID: 4399833

Abstract

Hybrids from a cross of rat hepatoma cells with diploid epithelial cells from rat liver have been studied with respect to karyotype and expression of two functions limited to the hepatoma parent: high level of the enzyme tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) and its inducibility with steroid hormones. The hybrids that contain the complete chromosomal complements from both parents show low enzyme activity and no inducibility. One hybrid clone, and all of its derivatives, which have lost 30-40% of the chromosomes initially present, show enzyme inducibility. Induction of tyrosine aminotransferase in the hepatoma and hybrid cells responds similarly to inhibition by cycloheximide and actinomycin D, and to steroid concentration. The enzymes from induced and noninduced hepatoma cells and from induced hybrid cells are similar in heat sensitivity and intracellular distribution; those from noninduced hybrid and diploid rat epithelial cells are different.

Keywords: dexamethasone, actinomycin D, chromosome numbers, logarithmic growth phase

Full text

PDF
3026

Selected References

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

  1. Attardi G., Parnas H., Hwang M. I., Attardi B. Giant-size rapidly labeled nuclear ribonucleic acid and cytoplasmic messenger ribonucleic acid in immature duck erythrocytes. J Mol Biol. 1966 Sep;20(1):145–182. doi: 10.1016/0022-2836(66)90123-9. [DOI] [PubMed] [Google Scholar]
  2. Davidson R. L., Ephrussi B., Yamamoto K. Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization. Proc Natl Acad Sci U S A. 1966 Nov;56(5):1437–1440. doi: 10.1073/pnas.56.5.1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Engel E., McGee B. J., Harris H. Recombination and segregation in somatic cell hybrids. Nature. 1969 Jul 12;223(5202):152–155. doi: 10.1038/223152a0. [DOI] [PubMed] [Google Scholar]
  4. Fellman J. H., Vanbellinghen P. J., Jones R. T., Koler R. D. Soluble and mitochondrial forms of tyrosine aminotransferase. Relationship to human tyrosinemia. Biochemistry. 1969 Feb;8(2):615–622. doi: 10.1021/bi00830a023. [DOI] [PubMed] [Google Scholar]
  5. Gelehrter T. D., Tomkins G. M. Control of tyrosine aminotransferase synthesis in tissue culture by a factor in serum. Proc Natl Acad Sci U S A. 1969 Oct;64(2):723–730. doi: 10.1073/pnas.64.2.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Granner D. K., Hayashi S., Thompson E. B., Tomkins G. M. Stimulation of tyrosine aminotransferase synthesis by dexamethasone phosphate in cell culture. J Mol Biol. 1968 Jul 28;35(2):291–301. doi: 10.1016/s0022-2836(68)80025-7. [DOI] [PubMed] [Google Scholar]
  7. Harris H., Miller O. J., Klein G., Worst P., Tachibana T. Suppression of malignancy by cell fusion. Nature. 1969 Jul 26;223(5204):363–368. doi: 10.1038/223363a0. [DOI] [PubMed] [Google Scholar]
  8. KENNEY F. T. Induction of tyrosine-alpha-ketoglutarate transaminase in rat liver. IV. Evidence for an increase in the rate of enzyme synthesis. J Biol Chem. 1962 Nov;237:3495–3498. [PubMed] [Google Scholar]
  9. Klebe R. J., Chen T., Ruddle R. H. Mapping of a human genetic regulator element by somatic cell genetic analysis. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1220–1227. doi: 10.1073/pnas.66.4.1220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McCormick W., Penman S. Regulation of protein synthesis in HeLa cells: translation at elevated temperatures. J Mol Biol. 1969 Jan;39(2):315–333. doi: 10.1016/0022-2836(69)90320-9. [DOI] [PubMed] [Google Scholar]
  11. Miller J. E., Litwack G. Purification, properties, and identity of liver mitochondrial tyrosine aminotransferase. J Biol Chem. 1971 May 25;246(10):3234–3240. [PubMed] [Google Scholar]
  12. PITOT H. C., PERAINO C., MORSE P. A., Jr, POTTER V. R. HEPATOMAS IN TISSUE CULTURE COMPARED WITH ADAPTING LIVER IN VIVO. Natl Cancer Inst Monogr. 1964 Apr;13:229–245. [PubMed] [Google Scholar]
  13. REUBER M. D. A transplantable bile-secreting hepatocellular carcinoma in the rat. J Natl Cancer Inst. 1961 Apr;26:891–899. [PubMed] [Google Scholar]
  14. Schneider J. A., Weiss M. C. Expression of differentiated functions in hepatoma cell hybrids. I. Tyrosine aminotransferase in hepatoma-fibroblast hybrids. Proc Natl Acad Sci U S A. 1971 Jan;68(1):127–131. doi: 10.1073/pnas.68.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Thompson E. B., Gelehrter T. D. Expression of tyrosine aminotransferase activity in somatic-cell heterokaryons: evidence for negative control of enzyme expression. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2589–2593. doi: 10.1073/pnas.68.10.2589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Thompson E. B., Granner D. K., Tomkins G. M. Superinduction of tyrosine aminotransferase by actinomycin D in rat hepatoma (HTC) cells. J Mol Biol. 1970 Dec 14;54(2):159–175. doi: 10.1016/0022-2836(70)90424-9. [DOI] [PubMed] [Google Scholar]
  17. Thompson E. B., Tomkins G. M., Curran J. F. Induction of tyrosine alpha-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc Natl Acad Sci U S A. 1966 Jul;56(1):296–303. doi: 10.1073/pnas.56.1.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tomkins G. M., Gelehrter T. D., Granner D., Martin D., Jr, Samuels H. H., Thompson E. B. Control of specific gene expression in higher organisms. Expression of mammalian genes may be controlled by repressors acting on the translation of messenger RNA. Science. 1969 Dec 19;166(3912):1474–1480. doi: 10.1126/science.166.3912.1474. [DOI] [PubMed] [Google Scholar]
  19. Weiss M. C., Todaro G. J., Green H. Properties of a hybrid between lines sensitive and insensitive to contact inhibition of cell division. J Cell Physiol. 1968 Feb;71(1):105–107. doi: 10.1002/jcp.1040710112. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES