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
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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