Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MRNA Expression Comparison Between Igfbp7-null and wild type mice at Lactation Day 3

ABSTRACT: Insulin like growth factor binding protein 7, Igfbp7, is a secreted protein that in addition to modulating insulin and insulin-like growth factor signaling, it acts as a tumor suppressor gene in breast and other cancers. To elucidate the role of Igfbp7 in regulating the proliferation and differentiation of mammary epithelial cells, we examined the growth and differentiation of mammary gland through different stages of its development in Igfbp7-null mice. Using transcriptome profiling in addition to functional assays we demonstrate that loss of Igfbp7 leads to diminished luminal cell differentiation and expansion of the luminal progenitors. These studies identify the endocrine factor Igfbp7, as a key regulator of luminal progenitor functions in the mammary gland. Mammary gland mRNA profiles of lactation day 3 wild type (WT) and Igfbp7-/- (KO) mice were generated by deep sequencing using SOLiD5500xl

ORGANISM(S): Mus musculus

SUBMITTER: Yutaka Amemiya

PROVIDER: E-GEOD-45118 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.

Chatterjee Sumanta S Bacopulos Stephanie S Yang Wenyi W Amemiya Yutaka Y Spyropoulos Demetri D Raouf Afshin A Seth Arun A

PloS one 20140204 2

<h4>Background</h4>Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals.<h ...[more]

PMID: 24505323

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Project description:GNAS, a gene encoding G-protein stimulating alpha subunit, is frequently mutated in intraductal papillary mucinous neoplasms (IPMNs), which is an indolent and slow-growing pancreatic neoplasm that secretes abundant mucin. GNAS mutation is not observed in conventional ductal adenocarcinomas of the pancreas. To determine the functional significance of GNAS mutation in pancreatic ductal cells, we examined in vitro phenotypes and gene expression profiles of cells of pancreatic ductal lineage, HPDE, PK-8, PCI-35, and MIA PaCa-2, with exogenous expression of either wild-type or mutated (R201H) GNAS. We found that exogenous GNAS upregulated intracellular cyclic-adenine monophosphate, particularly in the mutated GNAS transfectants. Exogenous GNAS induced no obvious cell-growth promotion, but induced suppression in some cells. The exogenous GNAS upregulated MUC2 and MUC5AC in HPDE and PK-8, and the latter was most sensitive to exogenous GNAS, exhibiting drastic alteration of the global gene expression that is consistent with that of IPMN. Hence, PK-8 expressing exogenous mutated GNAS may be an ideal in vitro model of IPMN. On the other hand, exogenous GNAS downregulated expression of mucin genes and produced modest alteration of gene expression profiles in PCI-35 and MIA PaCa-2, indicating lower sensitivity to exogenous GNAS. Furthermore, we showed diverse and cell-type specific mucin expression pathways with complicated interactions between signaling pathways of the G-protein coupled receptor (GPCR), the mitogen-activated protein kinase (MAPK), and the phosphatidylinositol 3 kinase (PI3K), in which the GPCR pathway appeared to be dominant in some and the MAPK pathway in others. In conclusion, mutated GNAS found in IPMNs may extensively alter gene expression profiles, including expression of mucin genes, with the interaction with MAPK and PI3K pathways in pancreatic ductal-lineage cells, which may determine the characteristic phenotype of the neoplasm. Cells of pancreatic cancer cell lines, PK-8, PCI-35,and MIA PaCa-2, were seeded at 4 M-CM-^W 10^5 cells/well in 6-well plates and incubated for 24 hours at 37M-BM-0C in 5% CO2 with humid atmosphere. Then the cells were transfected with either pcDNA 3.1/V5-His vector or pcDNA3.1-GNAS(R201H)-V5-His vector using Lipofectamine 2000 reagent (Life Technologies) according to the manufacturerM-bM-^@M-^Ys recommendations. The cells were incubated for 24 hours and collected by dissociation using trypsin. Total RNAs were isolated using the RNeasy Mini kit (Qiagen, Hilden, Germany). Serial analysis of gene expression (SAGE) library was constructed using a SOLiD SAGE Kit (Life Technologies) according to the manufactureM-bM-^@M-^Ys instruction. The constructed libraries were analysed by means of the massively parallel sequencing method using SOLiD 4 System (Life Technologies). The SAGE analysis was performed for samples obtained from single transfection experiment.

Dataset Information

MRNA Expression Comparison Between Igfbp7-null and wild type mice at Lactation Day 3

Publications

Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.

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