Methods of using the A form of the progesterone receptor to scre

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

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435 8, 435 691, 4352402, 435810, 935 33, 935 34, 935 36, C12Q 168

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055061028

ABSTRACT:
Methods to screen for antagonists of steroid IR transcription as mediated by the PR-A isoform of the progesterone receptor are provided. Such cell-based methods include a cell in which PR-A is transcriptionally inactive containing asteroid IR other than PR, PR-A and a reporter vector that includes a promoter which is transcriptionally active in the presence of the steroid IR and an activator of said steroid IR, but is substantially transcriptionally inactive in the presence of PR-A. This cell is contacted with the activator of the steroid IR and a compound to be assayed, and the level of reporter product produced in the cell is measured and compared to the level of reporter product expressed in a similar cellular system absent PR-A as an indication of the potential antagonist activity of the compound being assayed. Also provided are an assay kit, a method of screening PR active compounds as ER antagonists and compounds that inhibit the transcriptional activity of asteroid IR in the presence of PR-A in a cellular context where PR-A is substantially transcriptionally inactive.

REFERENCES:
patent: 4981784 (1991-01-01), Evans et al.
patent: 5071773 (1991-12-01), Evans et al.
patent: 5262300 (1993-11-01), Evans et al.
Poletti et al., Gene 114, 51-58 (1992).
McDonnell et al., J. Biol. Chem. 269(16), 11945-11949 (1994).
McDonnell et al., J. Steroid Biochem. Molec. Biol. 48(5/6), 425-432 (1994).
Vegeto et al., Molecular Endocrinology 7(10), 1244-1255 (1993).
Kastner, P., et al., "Two Distinct Estrogen-Regulated Promoters Generate Transcripts Encoding the Two Functionally Different Human Progesterone Receptor Forms A and B," The EMBO Journal, (1990) vol. 9, No. 5, pp. 1603-1614.
Meyer, Marc-Etienne et al., "Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor," The EMBO Journal, (1990) vol. 9, No. 12, pp. 3923-3932.
Lessey, Bruce A., et al., "The Subunit Structure of Human Breast Cancer Progesterone Receptors: Characterization by Chromatography and Photoaffinity Labeling," Endocrinology, (1983), vol. 112, No. 4, pp. 1267-1274.
Horwitz, Kathryn B., et al., "In Situ Photolinked Nuclear Progesterone Receptors of Human Breast Cancer Cells: Subunit Molecular Weights after Transformation and Translocation," Endocrinology, (1983) vol. 113, No. 6, pp. 2195-2201.
O'Malley, Bert, "The Steroid Receptor Superfamily: More Excitement Predicted for the Future," Molecular Endocrinology, (1990) vol. 4, No. 3, pp. 363-369.
Tora, Laszlo, et al., "The N-terminal region of the chicken progesterone receptor specifies target gene activation," Nature, (1988) vol. 333, pp. 185-188.
Takimoto, Glenn S., et al., "Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: Analysis with zinc finger mutants and the progesterone antagonist ZK98299," Proc. Natl. Acad. Sci. USA, (1992) vol. 89, pp. 3050-3054.
Klein-Hitpass, Ludger, et al., "Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells," Nucleic Acids Research, (1991) vol. 19, No. 6, pp. 1227-1234.
Clarke, C. L., et al., "Progestin Regulation of Cellular Proliferation," 11 Endocrine Rev., 266-301 (1990).
Conneely, O. M., et al., "The A and B Forms of the Chicken Progesterone Receptor Arise by Alternate Initiation of Translation of a Unique mRNA," Biochem. Bioph. Res. Comm., 493-501 (1987).
Christensen, K., et al., "Characterization and Functional Properties of the A and B forms of Human Progesterone Receptors Synthesized in a Baculovirus System," 5 Mol. Endocrinol. 1755-1770 (1991).
Klein-Hitpass, L., et al., "The Progesterone Receptor Stimulates Cell-free Transcription by Enhancing the Formation of a Stable Pre-initiation Complex," 60 Cell, 247-257 (1990).
Bocquel, M. T., et al., "The Contribution of the N-- and C--terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific," Nucleic Acids Research, (1989) vol. 17, No. 7, pp. 2581-2595.
Evans, Ronald M., "The Steroid and Thyroid Hormone Receptor Superfamily," Science,(1989) vol. 240, pp. 889-895.
Beato, Miguel, "Gene Regulation by Steroid Hormones," Cell, (1989) vol. 56, pp. 335-344.
Schrader, William T., et al., "Progesterone-binding Components of Chick Oviduct," The Journal of Biological Chemistry, (1972) vol. 247, No. 1, pp. 51-59.
Meyer, Marc-Etienne, et al., "A Limiting Factor Mediates the Differential Activation of Promoters by the Human Progesterone Receptor Isoforms," The Journal of Biological Chemistry, (1992) vol. 267, No. 15, pp. 10882-10887.
Berger, Tina S., et al., "Interaction of Glucocorticoid Analogues with the Human Glucocorticoid Receptor," J. Steroid Biochem. Molec. Biol. (1992) vol. 41, No. 3-8, pp. 733-738.
Shemshedini, Lirim, et al., "In Vitro Activity of the Transcription Activation Functions of the Progesterone Receptor, Evidence for Intermediary Factors," The Journal of Biological Chemistry, (1992) vol. 267, No. 3, pp. 1834-1839.
Vegeto, Elisabetta, et al., "The Mechanism of RU486 Antagonism is Dependent on the Conformation of the Carboxy-Terminal Tail of the Human Progesterone Receptor," Cell, (1992) vol. 69, pp. 703-713.

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