Abstract
We have introduced the rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector. The ability of the viral DNA to induce foci in the recipient cells was used as a dominant selection marker. Several copies of rat growth hormone DNA were integrated in the mouse cells. The transformed mouse cells expressed rat growth hormone-specific mRNA and secreted mature rat growth hormone. In rat cells, the expression of this gene is regulated by glucocorticoids. We demonstrate that hormone-dependent regulation transfers with the clone and thus appears to be an intrinsic property of the gene or its RNA products.
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Selected References
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- Barta A., Richards R. I., Baxter J. D., Shine J. Primary structure and evolution of rat growth hormone gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4867–4871. doi: 10.1073/pnas.78.8.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buetti E., Diggelmann H. Cloned mouse mammary tumor virus DNA is biologically active in transfected mouse cells and its expression is stimulated by glucocorticoid hormones. Cell. 1981 Feb;23(2):335–345. doi: 10.1016/0092-8674(81)90129-x. [DOI] [PubMed] [Google Scholar]
- Dobner P. R., Kawasaki E. S., Yu L. Y., Bancroft F. C. Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear precursor in rat pituitary cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2230–2234. doi: 10.1073/pnas.78.4.2230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fallon R. J., Cox R. P. Relation of cell cycle position and chromatin decondensation to ectopic hormone synthesis in HeLa cells. Somatic Cell Genet. 1981 Mar;7(2):193–204. doi: 10.1007/BF01567657. [DOI] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Harpold M. M., Dobner P. R., Evans R. M., Bancroft F. C. Construction and identification by positive hybridization-translation of a bacterial plasmid containing a rat growth hormone structural gene sequence. Nucleic Acids Res. 1978 Jun;5(6):2039–2053. doi: 10.1093/nar/5.6.2039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harpold M. M., Dobner P. R., Evans R., Bancroft F. C., Darnell J. E., Jr The synthesis and processing of a nuclear RNA precursor to rat pregrowth hormone messenger RNA. Nucleic Acids Res. 1979 Jul 11;6(9):3133–3144. doi: 10.1093/nar/6.9.3133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones M., Bosselman R. A., van der Hoorn F. A., Berns A., Fan H., Verma I. M. Identification and molecular cloning of Moloney mouse sarcoma virus-specific sequences from uninfected mouse cells. Proc Natl Acad Sci U S A. 1980 May;77(5):2651–2655. doi: 10.1073/pnas.77.5.2651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurtz D. T. Hormonal inducibility of rat alpha 2u globulin genes in transfected mouse cells. Nature. 1981 Jun 25;291(5817):629–631. doi: 10.1038/291629a0. [DOI] [PubMed] [Google Scholar]
- Lai E. C., Woo S. L., Bordelon-Riser M. E., Fraser T. H., O'Malley B. W. Ovalbumin is synthesized in mouse cells transformed with the natural chicken ovalbumin gene. Proc Natl Acad Sci U S A. 1980 Jan;77(1):244–248. doi: 10.1073/pnas.77.1.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee F., Mulligan R., Berg P., Ringold G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature. 1981 Nov 19;294(5838):228–232. doi: 10.1038/294228a0. [DOI] [PubMed] [Google Scholar]
- Leys E. J., Kellems R. E. Control of dihydrofolate reductase messenger ribonucleic acid production. Mol Cell Biol. 1981 Nov;1(11):961–971. doi: 10.1128/mcb.1.11.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maki R., Roeder W., Traunecker A., Sidman C., Wabl M., Raschke W., Tonegawa S. The role of DNA rearrangement and alternative RNA processing in the expression of immunoglobulin delta genes. Cell. 1981 May;24(2):353–365. doi: 10.1016/0092-8674(81)90325-1. [DOI] [PubMed] [Google Scholar]
- Mantei N., Boll W., Weissmann C. Rabbit beta-globin mRNA production in mouse L cells transformed with cloned rabbit beta-globin chromosomal DNA. Nature. 1979 Sep 6;281(5726):40–46. doi: 10.1038/281040a0. [DOI] [PubMed] [Google Scholar]
- Martial J. A., Seeburg P. H., Guenzi D., Goodman H. M., Baxter J. D. Regulation of growth hormone gene expression: synergistic effects of thyroid and glucocorticoid hormones. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4293–4295. doi: 10.1073/pnas.74.10.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Page G. S., Smith S., Goodman H. M. DNA sequence of the rat growth hormone gene: location of the 5' terminus of the growth hormone mRNA and identification of an internal transposon-like element. Nucleic Acids Res. 1981 May 11;9(9):2087–2104. doi: 10.1093/nar/9.9.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pellicer A., Robins D., Wold B., Sweet R., Jackson J., Lowy I., Roberts J. M., Sim G. K., Silverstein S., Axel R. Altering genotype and phenotype by DNA-mediated gene transfer. Science. 1980 Sep 19;209(4463):1414–1422. doi: 10.1126/science.7414320. [DOI] [PubMed] [Google Scholar]
- Potter E., Nicolaisen A. K., Ong E. S., Evans R. M., Rosenfeld M. G. Thyrotropin-releasing hormone exerts rapid nuclear effects to increase production of the primary prolactin mRNA transcript. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6662–6666. doi: 10.1073/pnas.78.11.6662. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenfeld M. G., Amara S. G., Roos B. A., Ong E. S., Evans R. M. Altered expression of the calcitonin gene associated with RNA polymorphism. Nature. 1981 Mar 5;290(5801):63–65. doi: 10.1038/290063a0. [DOI] [PubMed] [Google Scholar]
- Samuels H. H., Tsai J. S. Thyroid hormone action in cell culture: domonstration of nuclear receptors in intact cells and isolated nuclei. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3488–3492. doi: 10.1073/pnas.70.12.3488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sargent T. D., Wu J. R., Sala-Trepat J. M., Wallace R. B., Reyes A. A., Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. doi: 10.1073/pnas.76.7.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Stow N. D., Wilkie N. M. An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. J Gen Virol. 1976 Dec;33(3):447–458. doi: 10.1099/0022-1317-33-3-447. [DOI] [PubMed] [Google Scholar]
- Verma I. M., Lai M. H., Bosselman R. A., McKennett M. A., Fan H., Berns A. Molecular cloning of unintegrated Moloney mouse sarcoma virus DNA in bacteriophage lambda. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1773–1777. doi: 10.1073/pnas.77.4.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu L. Y., Tushinski R. J., Bancroft F. C. Glucocorticoid induction of growth hormone synthesis in a strain of rat pituitary cells. J Biol Chem. 1977 Jun 10;252(11):3870–3875. [PubMed] [Google Scholar]