Regulation of gene expression by PRA-910, a novel progesterone receptor modulator, in T47D cells
Autor: | Jeffrey D. Bray, C.Richard Lyttle, Richard C. Winneker, Zhiming Zhang |
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Rok vydání: | 2003 |
Předmět: |
Receptors
Steroid medicine.medical_specialty Time Factors animal structures medicine.drug_class Clinical Biochemistry Breast Neoplasms Biology Heterocyclic Compounds 2-Ring Biochemistry Endocrinology Cell Line Tumor Internal medicine Nitriles Gene expression Progesterone receptor polycyclic compounds medicine Humans skin and connective tissue diseases Molecular Biology Gene Oligonucleotide Array Sequence Analysis Pharmacology Regulation of gene expression Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Organic Chemistry Alkaline Phosphatase Gene expression profiling Mifepristone Gene Expression Regulation Models Chemical Mechanism of action Cancer research Gene chip analysis Female medicine.symptom Receptors Progesterone Progestin hormones hormone substitutes and hormone antagonists |
Zdroj: | Steroids. 68:995-1003 |
ISSN: | 0039-128X |
Popis: | Progestins play an important role in women’s health and are used in oral contraception, hormone therapy, and treatment of reproductive disorders. The effects of progestins upon gene expression in breast epithelium are poorly understood. In an attempt to characterize the molecular mechanism of progestin action, we used a gene expression profiling approach to examine the action of a novel progestin in the T47D cell model, a human breast cancer cell line. PRA-910 is a novel, nonsteroidal progesterone receptor modulator (PRM) with species-specific activities identified in a screen for selective PRMs. To understand the mechanism of action for PRA-910 in T47D cells, we compared its gene regulation to progesterone (P4) and RU486 through Affymetrix U95A GeneChip ® analysis and TaqMan RT–PCR. PRA-910, P4, and RU486 regulated 50, 108, and 16 genes by threefold or greater versus vehicle, respectively, with 18 genes having similar regulation for P4 and PRA-910. These data confirm and extend previous findings for T47D cells. We also obtained time course, concentration–response, cyclohexamide sensitivity, and PR-specificity data for two progestin-regulated genes, ATP1A1 and CLDN8 . Our data demonstrate that PRA-910 has a unique gene regulation profile distinct from both P4 and RU486. Further investigation of the underlying mechanism for these differences is ongoing. |
Databáze: | OpenAIRE |
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