Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The gene profile analysis of the function of HMGA2 in immortalized human ovarian surface epithelial cell lines.

ABSTRACT: To identify HMGA2-regulated downstream target genes, we compared the difference of gene profiles between ovarian surface epithelial cells without HMGA2 (T29-1, T29-2, T80) and cells with HMGA2 (T29A2-8, T29A2-15, T80A2-11). Immortalized ovarian surface epithelial cells (named T29-1, T29-2, T80) were transfected with HMGA2 retrovirus vector pBabe-HMGA2 (named T29A2-8, T29A2-15, T80A2-11). Then cells were harvested for RNA isolation for gene expression analysis. Control group: T29-1, T29-2, T80. Testing group: T29A2-8, T29A2-15, T80A2-11.

ORGANISM(S): Homo sapiens

SUBMITTER: Jingjing Wu

PROVIDER: E-GEOD-23599 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: Core 3 derived glycans, a major type of O-glycan expressed by normal epithelial cells of the gastrointestinal tract, are downregulated during malignancy, because of loss of expression of functional β3-N-acetylglucosaminyltransferase-6 (core 3 synthase). We investigated the expression of core 3 synthase in normal pancreas and pancreatic cancer and evaluated the biological effects of re-expressing core 3 synthase in pancreatic cancer cells that had lost expression. Experimental Design: We determined that pancreatic tumors and tumor cell lines have lost expression of core 3 synthase. We therefore re-expressed in human pancreatic cancer cells (Capan-2 and FG) to investigate the contribution of core 3 glycans to malignant progression. Results: Pancreatic cancer cells expressing core 3 synthase showed reduced in vitro cell proliferation, migration and invasion compared with vector control cells. Expression of core 3 O-glycans induced altered expression of β1 integrin, decreased activation of focal adhesion kinase, led to the down regulation of expression of several genes including REG1α and FGFR3, and altered lamellipodia formation. The addition of a GlcNAc residue by core 3 synthase leads to the extension of the tumor associated Tn structure on MUC1. Orthotopic injection of FG cells expressing core 3 synthase into the pancreas of nude mice produced significantly smaller tumors and decreased metastasis to the surrounding tissues compared to vector control FG cells. Conclusions: These findings indicate that expression of core 3 derived O-glycans in pancreatic cancer cells suppresses tumor growth and metastasis through modulation of glycosylation of mucins and other cell surface and extracellular matrix proteins. Two-condition experiment, Core 3 synthase stable expression (C3) vs. vector control (PLVX) cells. Biological replicates: 3 Core 3 synthase stable expression, 3 vector control, independently grown and harvested. One replicate per array.

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The gene profile analysis of the function of HMGA2 in immortalized human ovarian surface epithelial cell lines.

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