Home LiteratureArticle Details
PMID: 2030942 Published · ppublish English Journal Article

Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells.

Nucleic acids research ·Vol. 19 ·No. 6 ·1991-03-25 ·Pages 1227-34

Klein-Hitpass L, Cato AC, Henderson D, Ryffel GU

Abstract

Transcriptionally active nuclear extracts from human breast carcinoma cells (T47D) were used to compare the action of progestins and several antiprogestins of the 11 beta-aryl substituted steroid series on the DNA-binding properties and the trans-activating potential of progesterone receptor (PR) in vitro. Using the gel-shift assay we identified a novel type of antiprogestin (ZK98299, type I), which in contrast to type II antiprogestins, including RU486, does not induce binding of PR to progesterone response elements (PREs). In competition experiments excess of type I antiprogestin inhibits induction of DNA binding of PR by progestins and type II antiprogestins suggesting that its binding to PR interferes with the formation of stable receptor dimers. Moreover, we demonstrate that the antagonistic action of ZK98299 can be fully mimicked in vitro by using cell-free nuclear extracts from T47D cells and a 'simple' test promoter. In contrast, type II antiprogestins known to induce certain promoters in vivo exert strong agonistic effects on in vitro transcription of the test template used.

MeSH Terms
Base Sequence Binding, Competitive DNA/metabolism Gonanes/pharmacology Humans Mifepristone/pharmacology Molecular Sequence Data Plasmids Progesterone/antagonists & inhibitors,metabolism Receptors, Progesterone/metabolism TATA Box Transcription, Genetic/drug effects Transcriptional Activation Tumor Cells, Cultured
Chemicals
Gonanes Receptors, Progesterone Mifepristone Progesterone DNA onapristone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Klein-Hitpass L
Institut für Zellbiologie, Universitätsklinikum Essen, FRG.
Cato A C
Henderson D
Ryffel G U
References (42)
42 references, click to expand
  1. A secreted glycoprotein induced by estrogen in human breast cancer cell lines.
    Cell. 1980 Jun;20(2):353-62 PMID: 7388945
  2. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B.
    EMBO J. 1990 May;9(5):1603-14 PMID: 2328727
  3. In situ photolinked nuclear progesterone receptors of human breast cancer cells: subunit molecular weights after transformation and translocation.
    Endocrinology. 1983 Dec;113(6):2195-201 PMID: 6685620
  4. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters.
    Nature. 1985 Feb 21-27;313(6004):706-9 PMID: 2983219
  5. The antiprogestin RU38 486: receptor-mediated progestin versus antiprogestin actions screened in estrogen-insensitive T47Dco human breast cancer cells.
    Endocrinology. 1985 Jun;116(6):2236-45 PMID: 4039656
  6. Factors involved in specific transcription by human RNA polymerase II: analysis by a rapid and quantitative in vitro assay.
    Proc Natl Acad Sci U S A. 1985 Jul;82(13):4394-8 PMID: 3925456
  7. New steroids with antiprogestational and antiglucocorticoid activities.
    Steroids. 1984 Oct;44(4):349-72 PMID: 6152725
  8. Viral enhancer activity in teratocarcinoma cells.
    Cold Spring Harb Symp Quant Biol. 1985;50:747-52 PMID: 3007013
  9. The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction.
    EMBO J. 1986 Sep;5(9):2237-40 PMID: 3023063
  10. A superfamily of potentially oncogenic hormone receptors.
    Nature. 1986 Dec 18-31;324(6098):615-7 PMID: 3025739
  11. Studies on the mechanisms of action of progesterone antagonists.
    J Steroid Biochem. 1986 Nov;25(5B):835-45 PMID: 3543502
  12. The hormone response element of the mouse mammary tumour virus DNA mediates the progestin and androgen induction of transcription in the proviral long terminal repeat region.
    EMBO J. 1987 Feb;6(2):363-8 PMID: 3034586
  13. Immunologic analysis of human breast cancer progesterone receptors. 1. Immunoaffinity purification of transformed receptors and production of monoclonal antibodies.
    Biochemistry. 1987 Sep 22;26(19):6250-62 PMID: 3689773
  14. A high-efficiency HeLa cell nuclear transcription extract.
    DNA. 1988 Jan-Feb;7(1):47-55 PMID: 3349904
  15. The steroid and thyroid hormone receptor superfamily.
    Science. 1988 May 13;240(4854):889-95 PMID: 3283939
  16. Differential gene activation by glucocorticoids and progestins through the hormone regulatory element of mouse mammary tumor virus.
    Cell. 1988 May 6;53(3):371-82 PMID: 2835167
  17. Interaction of the antioestrogen ICI 164,384 with the oestrogen receptor.
    J Steroid Biochem. 1988;30(1-6):263-6 PMID: 3386250
  18. A rapid method of epitope mapping. Application to the study of immunogenic domains and to the characterization of various forms of rabbit progesterone receptor.
    Eur J Biochem. 1988 Sep 1;176(1):53-60 PMID: 2458256
  19. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer.
    Cell. 1988 Oct 7;55(1):145-56 PMID: 3167974
  20. Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation.
    Cell. 1988 Oct 21;55(2):361-9 PMID: 3167984
  21. Receptors bound to antiprogestin from abortive complexes with hormone responsive elements.
    Nature. 1988 Dec 15;336(6200):695-8 PMID: 3200320
  22. Identification of a functional intermediate in receptor activation in progesterone-dependent cell-free transcription.
    Nature. 1990 Jun 7;345(6275):547-50 PMID: 2348863
  23. Repression of the alpha-fetoprotein gene promoter by progesterone and chimeric receptors in the presence of hormones and antihormones.
    Mol Cell Biol. 1990 Sep;10(9):5002-6 PMID: 1697036
  24. Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6883-7 PMID: 2395882
  25. Reduced levels of hsp90 compromise steroid receptor action in vivo.
    Nature. 1990 Nov 8;348(6297):166-8 PMID: 2234079
  26. Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor.
    EMBO J. 1990 Dec;9(12):3923-32 PMID: 2249658
  27. Steroid hormone-dependent interaction of human progesterone receptor with its target enhancer element.
    Mol Endocrinol. 1988 Dec;2(12):1221-9 PMID: 3216861
  28. Gene regulation by steroid hormones.
    Cell. 1989 Feb 10;56(3):335-44 PMID: 2644044
  29. Liver cell specific gene transcription in vitro: the promoter elements HP1 and TATA box are necessary and sufficient to generate a liver-specific promoter.
    Nucleic Acids Res. 1989 Feb 11;17(3):939-53 PMID: 2922278
  30. Specific binding of estrogen receptor to the estrogen response element.
    Mol Cell Biol. 1989 Jan;9(1):43-9 PMID: 2927397
  31. Antitumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and the MNU-induced mammary tumor models of the rat.
    Eur J Cancer Clin Oncol. 1989 Apr;25(4):691-701 PMID: 2497018
  32. Antiprogestins, a new form of endocrine therapy for human breast cancer.
    Cancer Res. 1989 Jun 1;49(11):2851-6 PMID: 2720645
  33. Steroid hormone receptors compete for factors that mediate their enhancer function.
    Cell. 1989 May 5;57(3):433-42 PMID: 2720778
  34. Cooperative binding of steroid hormone receptors contributes to transcriptional synergism at target enhancer elements.
    Cell. 1989 May 5;57(3):443-8 PMID: 2566384
  35. Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers.
    Cell. 1989 Jun 30;57(7):1147-54 PMID: 2736623
  36. Contragestion and other clinical applications of RU 486, an antiprogesterone at the receptor.
    Science. 1989 Sep 22;245(4924):1351-7 PMID: 2781282
  37. Antitumor activity of the antiprogestins ZK 98.299 and RU 38.486 in hormone dependent rat and mouse mammary tumors: mechanistic studies.
    Breast Cancer Res Treat. 1989 Dec;14(3):275-88 PMID: 2514814
  38. The progesterone receptor stimulates cell-free transcription by enhancing the formation of a stable preinitiation complex.
    Cell. 1990 Jan 26;60(2):247-57 PMID: 2153462
  39. The antitumor mechanism of progesterone antagonists is a receptor mediated antiproliferative effect by induction of terminal cell death.
    J Steroid Biochem. 1989;34(1-6):447-53 PMID: 2626038
  40. Regulation of gene expression by nuclear hormone receptors.
    Curr Opin Cell Biol. 1989 Jun;1(3):503-11 PMID: 2560655
  41. Progesterone receptor stimulates transcription of mouse mammary tumour virus in a cell-free system.
    Nature. 1990 Mar 22;344(6264):360-2 PMID: 2156171
  42. [The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy].
    C R Seances Acad Sci III. 1982 May 17;294(18):933-8 PMID: 6814714
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/19.6.1227
Published
1991-03-25
Pages
1227-34
Language
English
Region
England
NLM ID
0411011
PMCID
PMC333847
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/19.6.1227 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2