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Expression data from GNMT knockout mice

ABSTRACT: We report that 7 of 7 female Gnmt-/- mice developed hepatocellular carcinoma (HCC), the most common form of liver cancer, at the mean age of 16.1 months. In contrast, only one-third (2/6) of male Gnmt-/- mice had HCC, the remaining had either premature death or liver necrosis. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: S-adenosylmethionine (SAM)-dependent methyltransferases, metabolism, signal transduction, cell proliferation, cell adhesion and immune responses. This study reveals that GNMT plays an important role in the prevention of hapatotumorigenesis through regulating DNA methylaiton and oxidative stress signaling pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Keywords: Gnmt knockout

ORGANISM(S): Mus musculus

PROVIDER: GSE9809 | GEO | 2008/12/01

SECONDARY ACCESSION(S): PRJNA103757

REPOSITORIES: GEO

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Expression data from GNMT knockout mice

Project description:We report that 7 of 7 female Gnmt-/- mice developed hepatocellular carcinoma (HCC), the most common form of liver cancer, at the mean age of 16.1 months. In contrast, only one-third (2/6) of male Gnmt-/- mice had HCC, the remaining had either premature death or liver necrosis. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: S-adenosylmethionine (SAM)-dependent methyltransferases, metabolism, signal transduction, cell proliferation, cell adhesion and immune responses. This study reveals that GNMT plays an important role in the prevention of hapatotumorigenesis through regulating DNA methylaiton and oxidative stress signaling pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Keywords: Gnmt knockout Liver tissues from wild-type or Gnmt knockout mice at young ages, devoloping dysplasia nodules or HCC were used for RNA extraction and hybridization on Affymetrix microarrays. For 11 weeks old mice, total RNA were mixed in equal proportion from 3 mice.

2008-12-01 | E-GEOD-9809 | biostudies-arrayexpress

Expression data from AFB1-treated GNMT knockout mice

Project description:We report that liver nodules from 5/8 (62.5%) male and 4/5 (80%) female Gnmt-/- mice were diagnosed as having HCC. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: Methylation, metabolism, signal transduction, cell proliferation, and cell adhesion. This study reveals that GNMT plays an important role in the prevention of hepatotumorigenesis through regulating detoxification pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer.

2009-10-02 | GSE18218 | GEO

Expression data from AFB1-treated GNMT knockout mice

2009-10-02 | E-GEOD-18218 | biostudies-arrayexpress

Expression data from GNMT knockout mice in Hepatocytes and OKER cell lines

Project description:Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients. Liver cirrhosis at a high risk of HCC has abnormal S-Adenosylmethionine (SAMe) levels. Catabolism of SAMe is mainly mediated by Glycine N-methyltransferase (GNMT), Lack in GNMT expression leads to epigenetic regulation of critical carcinogenesis pathways and mounting evidence assigns an essential role of GNMT in HCC. Methods: Here we have studied the role of LKB1-AMPK and RAS in the proliferation and transformation of GNMT-deficient HCC. Results. GNMT-deficient HCC was characterized by LKB1-AMPK misconnection, leading to resistance of apoptosis response mediated by a positive regulation of cAMP-PKA-CaMKKβ cascade. Additionally, Ras-mediated hyperactivation of LKB1 contributes to the proliferation of GNMT-deficient HCC in an ERK/p90RSK-dependent manner. The observed LKB1-induced Ras activation, was due to the regulation of RASGRP3 expression. Notably, the human HCC tumors with poorer prognosis showed the lowest levels of GNMT, p-AMPKα(Thr172) and the highest activation of Ras/LKB1/RASGRP3 axis. The present data suggest a correlation between LKB1 and RAS activity in a context of HCC with low GNMT expression, indicating that activation of the RAS/LKB1/RASGRP3 cascade might possess an important prognostic role in human liver cancer. Furthermore, these findings open the possibility to design new therapeutic strategies for the treatment of liver cancer.

2012-07-01 | GSE34838 | GEO

Expression data from GNMT knockout mice in Hepatocytes and OKER cell lines

Project description:Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients. Liver cirrhosis at a high risk of HCC has abnormal S-Adenosylmethionine (SAMe) levels. Catabolism of SAMe is mainly mediated by Glycine N-methyltransferase (GNMT), Lack in GNMT expression leads to epigenetic regulation of critical carcinogenesis pathways and mounting evidence assigns an essential role of GNMT in HCC. Methods: Here we have studied the role of LKB1-AMPK and RAS in the proliferation and transformation of GNMT-deficient HCC. Results. GNMT-deficient HCC was characterized by LKB1-AMPK misconnection, leading to resistance of apoptosis response mediated by a positive regulation of cAMP-PKA-CaMKKM-NM-2 cascade. Additionally, Ras-mediated hyperactivation of LKB1 contributes to the proliferation of GNMT-deficient HCC in an ERK/p90RSK-dependent manner. The observed LKB1-induced Ras activation, was due to the regulation of RASGRP3 expression. Notably, the human HCC tumors with poorer prognosis showed the lowest levels of GNMT, p-AMPKM-NM-1(Thr172) and the highest activation of Ras/LKB1/RASGRP3 axis. The present data suggest a correlation between LKB1 and RAS activity in a context of HCC with low GNMT expression, indicating that activation of the RAS/LKB1/RASGRP3 cascade might possess an important prognostic role in human liver cancer. Furthermore, these findings open the possibility to design new therapeutic strategies for the treatment of liver cancer. HCC induced wild-type or Gnmt knockout mice at 3 weeks old were used for RNA extraction and hybridization on Illumina microarrays. The study comprises three groups of samples: OKER cell line(n=3), GNMT-KO mouse hepatocytes (n=3) ,GNMT-WT mouse hepatocytes(n=3)

2012-06-30 | E-GEOD-34838 | biostudies-arrayexpress

Expression data from GNMT and MAT1A knockout models that develop all the stages of non-alcoholic fatty liver disease including hepatocellular carcinoma [GNMT_MAT1A_3&8_months]

Project description:Liver global gene expression patterns of 9 GNMT-knockout mice histopathologically determined to have non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) together with 10 MAT1A-knockout mice histopathologically determined to have steatosis and NASH. All these have their respective wild type patterns. These were analyzed to define signatures to study the pathogenesis of NAFLD-derived HCC, explore which subtypes of cancers can be investigated using mouse models and define a signature of HCC differential survival that can be used to characterize HCC subtypes of different survival derived from mixed etiologies.

2014-11-07 | GSE63027 | GEO

Expression data from GNMT knockout mice cerebral cortex

2011-09-01 | GSE23937 | GEO

Expression data from GNMT knockout mice cerebral cortex

Project description:We report that Gnmt-/- mice have abnormal behavior including spontaneous locomotion activity, PPI, TST and FST. Microarray analysis showed that genes expression profiles in male Gnmt -/- mice Keywords: Gnmt knockout Cerebral cortex tissues from wild-type or Gnmt knockout mice were used for RNA extraction and hybridization on Affymetrix microarrays. For 4 weeks old mice, total RNA were mixed in equal proportion from 3 mice.

2011-08-31 | E-GEOD-23937 | biostudies-arrayexpress

Establishment and characterization of a new murine cell line of sarcomatoid hepatocellular carcinoma

Project description:Sarcomatoid HCC is a rare and highly malignant type of HCC. A mouse cell line, Ymac-1 was established as a cell model of sarcomatoid HCC. The finding of this study could be useful for developing biomarkers and therapeutic modalities for sarcomatoid HCC. We used microarrays to delineate the mechnism of action of sarcomatoid HCC in normal mice liver, Gnmt-/- mice liver tumor, and Ymac-1 cell.

2017-06-23 | GSE88827 | GEO

RAS-dependent LKB1 hyperactivation in GNMT-deficient hepatocellular carcinoma

Project description:Xenograft model formed by OKER cells (GNMT-KO tumor cell line) in nude mice left flank, treated with siLKB1 by IP injection.

2012-10-11 | E-MEXP-3403 | biostudies-arrayexpress