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. 1987 Jun;6(6):1727–1731. doi: 10.1002/j.1460-2075.1987.tb02424.x

Hepatoma variants (C2) are defective for transcriptional and post-transcriptional actions from both endogenous and viral genomes.

J M Friedman, L E Babiss, M Weiss, J E Darnell Jr
PMCID: PMC553548  PMID: 2956094

Abstract

A series of rat hepatoma cell lines was infected with a recombinant adenovirus bearing the rat albumin promoter. Transcription from this promoter was scored directly and was highest in FAO, the differentiated parent, undetectable in C2, a cell variant that has lost almost all hepatocytic characteristics, and high again in C2-Rev7, a 'revertant' cell line derived from C2 that has regained the ability to produce many proteins characteristic of hepatocytes. The endogenous albumin gene is not transcribed in C2 cells, and at a very low rate in C2-Rev7 cells, which accumulate endogenous albumin mRNA at close to normal amounts. Thus the C2-Rev7 'recovery' of albumin mRNA concentration for the endogenous gene is based mainly on post-transcriptional events while the ability of C2-Rev7 to transcribe the albumin promoter in the viral genome is based on a transcriptional factor(s). We also showed that the C2 phenotype included post-transcriptional effects for other genes: transcription of phenylalanine hydroxylase and phosphoenolpyruvate carboxykinase mRNA sequences continue in C2 at rates equivalent to FAO but these C2 cells have no mRNA for these proteins while FAO does. In addition, C2 cells transcribed certain early adenovirus transcription units (E2 and 4) as well as FAO cells but accumulated E2 mRNAs poorly if at all. The changes that led to the C2-Rev7 cell line produced a return to normal of the ability to accumulate these viral mRNAs. Thus a major event in the C2 to C2-Rev7 transition involves post-transcriptional processes as well as the ability to transcribe the albumin promoter positioned in the virus genome.

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Selected References

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

  1. Babiss L. E., Friedman J. M., Darnell J. E., Jr Cellular promoters incorporated into the adenovirus genome. Effect of viral DNA replication on endogenous and exogenous gene transcription. J Mol Biol. 1987 Feb 20;193(4):643–650. doi: 10.1016/0022-2836(87)90347-0. [DOI] [PubMed] [Google Scholar]
  2. Babiss L. E., Friedman J. M., Darnell J. E., Jr Cellular promoters incorporated into the adenovirus genome: effects of viral regulatory elements on transcription rates and cell specificity of albumin and beta-globin promoters. Mol Cell Biol. 1986 Nov;6(11):3798–3806. doi: 10.1128/mcb.6.11.3798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blobel G. Gene gating: a hypothesis. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8527–8529. doi: 10.1073/pnas.82.24.8527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cassio D., Weiss M. C., Ott M. O., Sala-Trepat J. M., Friès J., Erdos T. Expression of the albumin gene in rat hepatoma cells and their dedifferentiated variants. Cell. 1981 Dec;27(2 Pt 1):351–358. doi: 10.1016/0092-8674(81)90418-9. [DOI] [PubMed] [Google Scholar]
  5. Clayton D. F., Darnell J. E., Jr Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol Cell Biol. 1983 Sep;3(9):1552–1561. doi: 10.1128/mcb.3.9.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clayton D. F., Weiss M., Darnell J. E., Jr Liver-specific RNA metabolism in hepatoma cells: variations in transcription rates and mRNA levels. Mol Cell Biol. 1985 Oct;5(10):2633–2641. doi: 10.1128/mcb.5.10.2633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  8. Coon H. G., Weiss M. C. A quantitative comparison of formation of spontaneous and virus-produced viable hybrids. Proc Natl Acad Sci U S A. 1969 Mar;62(3):852–859. doi: 10.1073/pnas.62.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  10. Deschatrette J., Moore E. E., Dubois M., Weiss M. C. Dedifferentiated variants of a rat hepatoma:reversion analysis. Cell. 1980 Apr;19(4):1043–1051. doi: 10.1016/0092-8674(80)90095-1. [DOI] [PubMed] [Google Scholar]
  11. Deschatrette J., Weiss M. C. Characterization of differentiated and dedifferentiated clones from a rat hepatoma. Biochimie. 1974;56(11-12):1603–1611. doi: 10.1016/s0300-9084(75)80286-0. [DOI] [PubMed] [Google Scholar]
  12. Enoch T., Zinn K., Maniatis T. Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Friedman J. M., Babiss L. E., Clayton D. F., Darnell J. E., Jr Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression. Mol Cell Biol. 1986 Nov;6(11):3791–3797. doi: 10.1128/mcb.6.11.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hart R. P., McDevitt M. A., Ali H., Nevins J. R. Definition of essential sequences and functional equivalence of elements downstream of the adenovirus E2A and the early simian virus 40 polyadenylation sites. Mol Cell Biol. 1985 Nov;5(11):2975–2983. doi: 10.1128/mcb.5.11.2975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hofer E., Darnell J. E., Jr The primary transcription unit of the mouse beta-major globin gene. Cell. 1981 Feb;23(2):585–593. doi: 10.1016/0092-8674(81)90154-9. [DOI] [PubMed] [Google Scholar]
  16. Hutchison N., Weintraub H. Localization of DNAase I-sensitive sequences to specific regions of interphase nuclei. Cell. 1985 Dec;43(2 Pt 1):471–482. doi: 10.1016/0092-8674(85)90177-1. [DOI] [PubMed] [Google Scholar]
  17. Ott M. O., Sperling L., Herbomel P., Yaniv M., Weiss M. C. Tissue-specific expression is conferred by a sequence from the 5' end of the rat albumin gene. EMBO J. 1984 Nov;3(11):2505–2510. doi: 10.1002/j.1460-2075.1984.tb02164.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. REUBER M. D. A transplantable bile-secreting hepatocellular carcinoma in the rat. J Natl Cancer Inst. 1961 Apr;26:891–899. [PubMed] [Google Scholar]
  20. Sargent T. D., Jagodzinski L. L., Yang M., Bonner J. Fine structure and evolution of the rat serum albumin gene. Mol Cell Biol. 1981 Oct;1(10):871–883. doi: 10.1128/mcb.1.10.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yoo-Warren H., Monahan J. E., Short J., Short H., Bruzel A., Wynshaw-Boris A., Meisner H. M., Samols D., Hanson R. W. Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3656–3660. doi: 10.1073/pnas.80.12.3656. [DOI] [PMC free article] [PubMed] [Google Scholar]

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