Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparison of Differences in Mouse Mammary gland gene expression data at POSTNATAL DAY 70 in Akt1wildtype versus Akt1-deficient mice

ABSTRACT: Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays a critical role in the regulation of several cellular processes including cell proliferation and apoptosis. In this study, we utilized Akt1+/+ and Akt1Â¬-/- C57/Bl6 female mice to demonstrate that Akt1 is required for normal mammary gland postnatal development and homeostasis. Akt1 deficiency resulted in severely delayed postnatal mammary gland growth as well as a significant decrease in the number of terminal end buds during puberty. Adult Akt1-/- mammary glands exhibited significantly fewer alveolar buds coupled with a significant increase in epithelial cell apoptosis compared to their wild-type counterparts. Microarray analysis revealed that Akt1 deficiency resulted in several altered gene expression changes and biological processes in adult mammary glands, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1-/- mammary glands by both microarray and RT-PCR validation. Transcriptome analysis of Akt1 wild type and akt1-homozygous mouse mammary glands wild type mammary glands from 3 mice and Akt1-deficient mammary glands from 3 mice were analyzed for differences in gene expression at postnatal day 70

ORGANISM(S): Mus musculus

SUBMITTER: Mary Hixon

PROVIDER: E-GEOD-30671 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1.

LaRocca Jessica J Pietruska Jodie J Hixon Mary M

PloS one 20110907 9

Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1-/- C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that p ...[more]

PMID: 21915327

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Project description:The present experiments were performed to determine the roles of estrogen receptors M-NM-1 and M-NM-2 (ERM-NM-1 and ERM-NM-2) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERM-NM-2 gene has been deleted (M-NM-2ERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERM-NM-1 gene has been deleted (M-NM-1ERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of M-NM-1ERKO mice: treatment of M-NM-1ERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G- protein-coupled receptor (GPR30) protein. Mammary gland development in M-NM-2ERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or M-NM-2ERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and M-NM-2ERKO mice, but failed to induce MAL in mammary glands from M-NM-1ERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in M-NM-1ERKO mice versus both M-NM-2ERKO and wild-type mice; key functions that were differentially expressed in M-NM-1ERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERM-NM-1 and ERM-NM-2 in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERM-NM-1-mediated effects of E in this organ. Gene expression of mammary gland organ culture and DMBA-induced lesions from 4 mouse strains.

Dataset Information

Comparison of Differences in Mouse Mammary gland gene expression data at POSTNATAL DAY 70 in Akt1wildtype versus Akt1-deficient mice

Publications

Akt1 is essential for postnatal mammary gland development, function, and the expression of Btn1a1.

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