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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.

ORGANISM(S): Mus musculus

PROVIDER: GSE45118 | GEO | 2014/09/02

SECONDARY ACCESSION(S): PRJNA193345

REPOSITORIES: GEO

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

Project description: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

2014-09-02 | E-GEOD-45118 | biostudies-arrayexpress

Insulin-like Growth Factor Binding Protein-7 (IGFBP7) regulation in Hepatocellular Carcinoma

Project description:Insulin like growth factor binding protein-7 (IGFBP7) inhibits IGF signaling and functions as a potential tumor suppressor for hepatocellular carcinoma (HCC). We profiled genome-wide gene expression of Igfbp7 knockout (Igfbp7-/-) mouse to demonstrate the constitutive activation of IGF signaling and its relationship to the accelerated carcinogen-induced HCC.

2019-08-01 | GSE85427 | GEO

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation

Project description:Integrin dimers α3/β1, α6/β1 and α6/β4 are the mammary epithelial cell receptors for laminins, which are major components of the basement membrane, a specialized extracellular matrix surrounding the mammary epithelium. The roles of specific basement membrane components and their integrin receptors in the regulation of functional gland development have not been analyzed in detail. To investigate the functions of laminin-binding integrins, we obtained mutant mice with mammary luminal cell-specific deficiencies of the α3 and α6 integrin chains generated by the Cre-Lox approach. During pregnancy, mutant mice displayed low levels of luminal progenitor activity and retarded lobulo-alveolar development, whereas their mammary glands seemed to be functional at the onset of lactation. Myoepithelial cell morphology was markedly altered in mutant glands, suggesting cellular compensation mechanisms involving cytoskeleton reorganization. However, lactation was not sustained in mutant mice, and the glands underwent precocious involution. Inactivation of the p53 gene rescued the growth defects but did not restore lactogenesis in mutant mice. This study reveals an essential role for laminin-binding integrins in functional mammary gland development.

2020-02-04 | GSE132281 | GEO

Gene expression in mammary glands of lactating wild-type or Th-POK-deficient mice.

Project description:The Th-inducing POK (Th-POK, also known as cKrox or ZBTB7B) transcription factor is a key regulator of lineage commitment of immature T cell precursors. It is yet unclear the physiological functions of Th-POK besides helper T cell differentiation. We found that Th-POK is restrictedly expressed in the luminal epithelial cells in the mammary glands. Th-POK is not required for mammary gland development in puberty and alveologenesis in pregnancy. Th-POK-deficient mice are defective in secretory activation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells. We compared microarray gene expression in mammary glands of lactating wild-type or Th-POK-deficient mice. We show that Th-POK directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling. Th-POK deficiency compromises IRS-1 expression and Akt-mTOR-SREBP signaling in the mammary glands. Thus, Th-POK function as an important regulator of insulin signaling in mammary gland lactation.

2018-02-06 | GSE97566 | GEO

Laminin-binding integrins are essential for the maintenance of functional secretory epithelium in lactation [luminal cells]

2020-02-04 | GSE132349 | GEO

Knockdown of IGFBP7 decreases FGF2 expression in GC.

Project description:Our previous study reported that IGFBP7 plays a role in maintaining mRNA stability of oncogenic lncRNA UBE2CP3 by RNA-RNA interaction. Clinical cohort studies had implied an oncogenic role of IGFBP7 in GC. However, the molecular mechanism of IGFBP7 in driving gastric cancer (GC) progression remains unknown. In this study, clinical analysis based on two independent cohort showed that IGFBP7 was positively associated with poor prognosis and macrophage infiltration in GC. Loss-of-function studies confirmed the oncogenic properties of IGFBP7 in regulating GC cell proliferation and invasion. Mechanismly, IGFBP7 was induced by epithelial-to-mesenchymal transition (EMT) signaling, since its expression was increased by TGF-beta treatment and reduced by overexpression of OVOL2 in GC. RNA sequencing, qRT-PCR, ELISA assay showed that IGFBP7 positively regulating FGF2 expression and secretion. Transcriptome analysis revealed that FGFR1 was downregulated in M1 macrophages but upregulated in M2 macrophages. Exogenous recombinant IGFBP7 protein in macrophages and GC cells further identified that IGFBP7 promotes macrophage polarization towards to a M2/TAM phenotype via FGF2/FGFR1/PI3K/AKT axis. Our finding highlights that IGFBP7 promotes GC by enhancing TAM infiltration through FGF2/FGFR1/PI3K/AKT axis.

2022-07-08 | GSE207373 | GEO

AP-2γ is Required for Maintenance of Multipotent Mammary Stem Cells

Project description:Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Herein, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors. AP-2γ regulated the expression of genes known to be required for mammary development including Cebpb, Nfkbia, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ can regulate development of mammary gland structures potentially regulating maintenance and differentiation of multipotent MaSCs.

2020-12-30 | GSE143159 | GEO

Transcription factor activator protein 2C (TFAP2C) regulates luminal differentiation in mammary development and carcinogenesis

Project description:Molecular subtypes of breast cancer are characterized by patterns of gene expression, which can be used to predict response to therapy and overall clinical outcome. The luminal breast cancer subtypes are defined by the expression of ER-alpha (ERa) and a set of ERa-associated genes. The transcription factor activator protein 2C (TFAP2C, AP-2C, AP-2g) transcription factor plays a critical role in regulating cell growth and differentiation during ectodermal development and has been implicated in the regulation of ERa and other luminal-associated genes in breast cancer. While TFAP2C has been established as a prognostic factor in human breast cancer, the role of TFAP2C in development of the luminal epithelial cells in the normal mammary gland and in breast cancer have remained elusive. Herein, we demonstrate a critical role of TFAP2C in maintaining the luminal differentiation phenotype during normal mammary development and in luminal breast carcinoma cell lines. Total RNA from MCF7 cells with and without knockdown of TFAP2c. 3 biological replicates, with 2 technical replicates each, were performed for each sample type.

2014-02-01 | E-GEOD-44203 | biostudies-arrayexpress

Transcription factor activator protein 2C (TFAP2C) regulates luminal differentiation in mammary development and carcinogenesis

2014-02-01 | GSE44203 | GEO

Expression data from sorted control and Pygo2-null mouse mammary stem/basal cells

Project description:Skin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development. The FACS sorted mammary stem cell (MaSC)/basal population from Pygo2 SSKO mammary gland displays biased differentiation towards luminal/alveolar lineage in vitro, and reduced regeneration rate of new mammary gland in vivo To gain the insight into gene expression profiles in control and Pygo2 SSKO mammary epithelial cells (MECs), we sorted the freshly isolated mouse MECs into MaSC/basal (Lin-CD29hiCD24+) and mature luminal population (Lin-CD29lowCD24+CD61-), and extract total RNA for cDNA microarray analysis

2013-09-05 | E-GEOD-45826 | biostudies-arrayexpress

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