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Gene expression analyses of PR action in the mammary gland of ovariectomized mice

ABSTRACT: Beyond demonstrating a critical role for progesterone receptor signaling in normal mammary epithelial proliferation, the progesterone receptor knockout mouse disclosed the progesterone receptor along with its effector pathways as key determinants of mammary neoplastic progression. Despite these advances, however, further progress in our mechanistic understanding of progesterone’s involvement in mammary morphogenesis and tumorigenesis is contingent upon defining the essential effector pathways responsible for transducing the progesterone signal into a mammary proliferative and/or pro-survival response. Toward this goal, a judiciously chosen acute progesterone treatment regimen together with microarray methods was applied to the mammary gland of the normal mouse to uncover new effectors that operate immediately downstream of the progesterone mammary signal. Examination of the resultant progesterone-responsive transcriptome disclosed “inhibitor of differentiation or DNA binding 4” (Id4) as a molecular target acutely induced by progesterone in the murine mammary epithelium. Keywords: time course

ORGANISM(S): Mus musculus

PROVIDER: GSE10290 | GEO | 2008/11/15

SECONDARY ACCESSION(S): PRJNA108501

REPOSITORIES: GEO

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Transcription profiling of mammary tissue from ovariectomized mice previously treated with progesterone for 4, 16, 28, and 76 hours

Project description:Beyond demonstrating a critical role for progesterone receptor signaling in normal mammary epithelial proliferation, the progesterone receptor knockout mouse disclosed the progesterone receptor along with its effector pathways as key determinants of mammary neoplastic progression. Despite these advances, however, further progress in our mechanistic understanding of progesteroneâ??s involvement in mammary morphogenesis and tumorigenesis is contingent upon defining the essential effector pathways responsible for transducing the progesterone signal into a mammary proliferative and/or pro-survival response. Toward this goal, a judiciously chosen acute progesterone treatment regimen together with microarray methods was applied to the mammary gland of the normal mouse to uncover new effectors that operate immediately downstream of the progesterone mammary signal. Examination of the resultant progesterone-responsive transcriptome disclosed â??inhibitor of differentiation or DNA binding 4â?? (Id4) as a molecular target acutely induced by progesterone in the murine mammary epithelium. Experiment Overall Design: Microarray analysis was performed on mammary tissue total RNA obtained from ovariectomized mice previously treated with progesterone for 4, 16, 28, and 76 hours. For each hormone treatment time-point, mammary gland microarray data from sesame oil (vehicle) treated mice was included as controls. Total mammary gland RNA from each time-point and treatment group was interrogated using the Affymetrix GeneChip Mouse Genome 430 2.0 Array. For a given time-point and treatment group, three sets of mice (5 mice in each set) were used for gene expression profiling; mammary RNA pooled from each set was hybridized to one microarray chip. Therefore, a total of 15 mice (or 3 microarray chips) were used per time-point and treatment group.

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