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Gene expression analysis of TGF-beta signaling-disrupting gastric cancer cell line 2MLN

ABSTRACT: Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However, detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE12336 | GEO | 2011/12/30

SECONDARY ACCESSION(S): PRJNA113229

REPOSITORIES: GEO

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Gene expression analysis of TGF-beta signaling-disrupting gastric cancer cell line 2MLN

Project description:Diffuse-type gastric carcinoma is a poor-prognostic cancer with high expression of transforming growth factor (TGF)-β and thick stromal fibrosis. However, detailed investigations on the roles of TGF-β signaling in diffuse-type gastric carcinoma have not been performed. We generated two diffuse-type gastric carcinoma cell lines, dominant-negative TGF-β type II receptor expressing cells (2MLN-dnTβRII) and GFP-expressing cells (2MLN-GFP). Cells were subcutaneously or orthotopically injected into nude mice. Although dnTβRII did not affect the growth of OCUM-2MLN in vitro, it accelerated the growth of subcutaneously or orthotopically transplanted tumors in vivo. By microarray analysis, we found gene expression of TSP-1, an angiogenic inhibitor, was down-regulated in dnTβRII tumors. This results suggested disruption of TGF-β signaling in diffuse-type gastric carcinoma cells leads to alteration of tumor microenvironment and acceleration of tumor growth. We generated two OCUM-2MLN-derived gastric carcinoma cell lines; 2MLN-dnTβRII, which expresses dominant negative form of TβRII, and control 2MLN-GFP, which expresses GFP. The transplanted tumors of these cell lines were subjected to gene expression analysis with Affymetrix U133 plus2 arrays.

2011-12-30 | E-GEOD-12336 | biostudies-arrayexpress

Expression profile of 58As9 cells upon PLEKHA5 knockdown

Project description:Phosphoproteomic analysis of diffuse-type gastric carcinoma cells with Met gene amplification identified Pleckstrin Homology Domain Containing A5 (PLEKHA5) as a protein that is tyrosine-phosphorylated downstream of Met. We used DNA microarray analysis to explore the signaling pathways downstream of PLEKHA5 that regulates the survival and peritoneal dissemination of Met-amplified 58As9 diffuse-type gastric carcinoma cells.

2020-12-12 | GSE163063 | GEO

Expression data from intestinal-type and diffuse-type gastric cancers

Project description:To identify the specific genes for intestinal-type and diffuse-type gastric cancers. We selected 18 intestinal-type gastric cancers and 12 diffuse-type gastric cancers showing typical characteristics on the form of cell growth (clustered or scattered) and the degree of differentiation (well/moderate or poor), and performed microarray analysis for obtaining genome-wide mRNA expression profiles.

2014-12-25 | E-GEOD-47007 | biostudies-arrayexpress

Low Expression of SP1 has a Different Effect on Intestinal-type compared to Diffuse-type Gastric Adenocarcinoma

Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma.

2012-01-01 | GSE34792 | GEO

Low Expression of SP1 has a Different Effect on Intestinal-type compared to Diffuse-type Gastric Adenocarcinoma

2012-01-01 | E-GEOD-34792 | biostudies-arrayexpress

Growth Factor Levels in the Blood of Patients Undergoing Radiation Therapy for Epithelial Cancer

Project description:RATIONALE: Measuring levels of transforming growth factor-beta (TGF-beta) in the blood of patients with epithelial cancers (head and neck, lung, breast, colorectal, and prostate) may help doctors predict how patients will respond to treatment with radiation therapy. PURPOSE: This research study is measuring levels of TGF-beta in patients with epithelial cancers who are undergoing radiation therapy.

| 2072028 | ecrin-mdr-crc

Gene expression profiling in hepatocellular carcinoma cell lines PRC/PRF/5 and SNU-449 after a treatment with Transforming Growth Factor beta (TGF-beta) and Galunisertib, alone or in combination

Project description:Transforming Growth Factor beta (TGF-beta) is a pleiotropic cytokine playing a key role in liver carcinogenesis. The goal of this study was to identify genes differentially expressed in hepatocellular carcinoma cell lines PRC/PRF/5 and SNU-449 after a treatment with TGF-beta and/or Galunisertib, an inhibitor of the type I TGF-beta receptor (TGFBRI). Thus, cells were treated for 16 hours with 1 ng/mL recombinant human TGF-β1 (R&D Systems, Minneapolis, MN) and/or 10 μM LY2157299 (Sigma-Aldrich, St. Louis, MO) after overnight serum starvation. Gene expression profiling was performed using Agilent SurePrint G3 Human GE 8x60K microarrays.

2023-06-01 | GSE211806 | GEO

Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells

Project description:Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Transforming growth factor beta (TGF-β) is highly expressed in the liver tumor microenvironment and is known to inhibit immune cell activity. Here, we used human iPSCs to produce natural killer (NK) cells engineered to mediate improved anti-HCC activity. Specifically, we produced iPSC-NK cells with either knock out TGF-β receptor 2 (TGFBR2-KO) or expression of a dominant negative (DN) form of the TGF-β receptor 2 (TGFBR2-DN) combined with CARs that target either GPC3 or AFP. The TGFBR2-KO and TGFBR2-DN iPSC-NK cells are resistant to TGF-β inhibition and improved anti-HCC activity. However, expression of anti-HCC CARs on iPSC-NK cells did not lead to effective anti-HCC activity unless there was also inhibition of TGF-b activity. Our findings demonstrate that TGF-β signaling blockade is required for effective NK cell function against HCC and potentially other malignancies which express high levels of TGF-β.

2024-04-08 | GSE263459 | GEO

Vicious circle of LSD1 and TGF Î²1 promotes EMT of gastric cancer

Project description:Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF Î²1) in gastric cancer tissues and can be promoted by TGF Î²1 activated (p-EKR)-(NF-ÎºB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF Î²1 as well as the EMT. But in benign cells, this circle was blocked by TGF Î²1 induced inactivation of ERK, which suggested the distinct roles of TGF Î²1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF Î²1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer. Nuclear extracts prepared from MGC803 cells stably expressing Lenti-CAS9-sgRNA-puro for LSD1 or empty vector were used in immunoprecipitation reactions with antibodies against H3K4me2 and H3K9me2. Sequencing libraries were prepared using the TruSeq DNA Sample Prep Kit (Illumina) and sequencing was performed on a HiSeq2000 (Illumina).

2016-07-19 | E-GEOD-84487 | biostudies-arrayexpress

Profiling of genes regulated by TGF-beta in immortalized skin keratinocyte cells(HaCaT).

Project description:TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. The effect of TGF-beta on the regulation of gene expression is cell-type specific. In order to identify TGF-beta regulated genes in different cell-types, we followed the expression profiling approach. Keywords: cell type specific response to TGF-beta

2007-05-01 | GSE7661 | GEO

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