Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Jan;67(1):99–101. doi: 10.1038/bjc.1993.16

Dexamethasone decreases urokinase plasminogen activator mRNA stability in MAT 13762 rat mammary carcinoma cells.

B R Henderson 1, R F Kefford 1
PMCID: PMC1968203  PMID: 8427785

Abstract

The glucocorticoid dexamethasone was observed to decrease urokinase plasminogen activator (uPA) RNA levels from within 1 h of treatment of MAT 13762 mammary adenocarcinoma cells. The drug did not alter the rate of uPA gene transcription in these cells, but decreased the stability of cytoplasmic uPA mRNA transcripts. Results from cycloheximide and actinomycin D experiments indicated that the dexamethasone-mediated reduction in uPA RNA required both new protein and RNA synthesis. Based on these results, we propose that dexamethasone induces a short-lived protein(s) which down-regulates uPA RNA levels post-transcriptionally in these metastatic tumour cells.

Full text

PDF

Images in this article

Selected References

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

  1. Altus M. S., Nagamine Y. Protein synthesis inhibition stabilizes urokinase-type plasminogen activator mRNA. Studies in vivo and in cell-free decay reactions. J Biol Chem. 1991 Nov 5;266(31):21190–21196. [PubMed] [Google Scholar]
  2. Altus M. S., Pearson D., Horiuchi A., Nagamine Y. Inhibition of protein synthesis in LLC-PK1 cells increases calcitonin-induced plasminogen-activator gene transcription and mRNA stability. Biochem J. 1987 Mar 1;242(2):387–392. doi: 10.1042/bj2420387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blasi F., Vassalli J. D., Danø K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol. 1987 Apr;104(4):801–804. doi: 10.1083/jcb.104.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Busso N., Belin D., Failly-Crépin C., Vassalli J. D. Plasminogen activators and their inhibitors in a human mammary cell line (HBL-100). Modulation by glucocorticoids. J Biol Chem. 1986 Jul 15;261(20):9309–9315. [PubMed] [Google Scholar]
  5. Busso N., Collart M., Vassalli J. D., Belin D. Antagonist effect of RU 486 on transcription of glucocorticoid-regulated genes. Exp Cell Res. 1987 Dec;173(2):425–430. doi: 10.1016/0014-4827(87)90282-5. [DOI] [PubMed] [Google Scholar]
  6. Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
  7. Henderson B. R., Kefford R. F. Conservation and potential role of RNA-instability motifs in urokinase gene 3'-untranslated sequences. J Natl Cancer Inst. 1991 Aug 7;83(15):1103–1104. doi: 10.1093/jnci/83.15.1103. [DOI] [PubMed] [Google Scholar]
  8. Henderson B. R., McDonald D. A., Kefford R. F. Post-transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells. Int J Cancer. 1992 Apr 1;50(6):918–923. doi: 10.1002/ijc.2910500617. [DOI] [PubMed] [Google Scholar]
  9. Henderson B. R., Tansey W. P., Phillips S. M., Ramshaw I. A., Kefford R. F. Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells. Cancer Res. 1992 May 1;52(9):2489–2496. [PubMed] [Google Scholar]
  10. Hentze M. W. Determinants and regulation of cytoplasmic mRNA stability in eukaryotic cells. Biochim Biophys Acta. 1991 Nov 11;1090(3):281–292. doi: 10.1016/0167-4781(91)90191-n. [DOI] [PubMed] [Google Scholar]
  11. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  12. Lee S. W., Tsou A. P., Chan H., Thomas J., Petrie K., Eugui E. M., Allison A. C. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1204–1208. doi: 10.1073/pnas.85.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Maroder M., Martinotti S., Vacca A., Screpanti I., Petrangeli E., Frati L., Gulino A. Post-transcriptional control of c-myc proto-oncogene expression by glucocorticoid hormones in human T lymphoblastic leukemic cells. Nucleic Acids Res. 1990 Mar 11;18(5):1153–1157. doi: 10.1093/nar/18.5.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Medcalf R. L., Van den Berg E., Schleuning W. D. Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2. J Cell Biol. 1988 Mar;106(3):971–978. doi: 10.1083/jcb.106.3.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mukaida N., Zachariae C. C., Gusella G. L., Matsushima K. Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. J Immunol. 1991 Feb 15;146(4):1212–1215. [PubMed] [Google Scholar]
  16. Peppel K., Vinci J. M., Baglioni C. The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids. J Exp Med. 1991 Feb 1;173(2):349–355. doi: 10.1084/jem.173.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rørth P., Nerlov C., Blasi F., Johnsen M. Transcription factor PEA3 participates in the induction of urokinase plasminogen activator transcription in murine keratinocytes stimulated with epidermal growth factor or phorbol-ester. Nucleic Acids Res. 1990 Sep 11;18(17):5009–5017. doi: 10.1093/nar/18.17.5009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schuler G. D., Cole M. D. GM-CSF and oncogene mRNA stabilities are independently regulated in trans in a mouse monocytic tumor. Cell. 1988 Dec 23;55(6):1115–1122. doi: 10.1016/0092-8674(88)90256-5. [DOI] [PubMed] [Google Scholar]
  19. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  20. Ziegler A., Hagmann J., Kiefer B., Nagamine Y. Ca2+ potentiates cAMP-dependent expression of urokinase-type plasminogen activator gene through a calmodulin- and protein kinase C-independent mechanism. J Biol Chem. 1990 Dec 5;265(34):21194–21201. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES