Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dysregulation of pathways involved in the processing of cancer and microenvironment information in MCA+TPA transformed C3H/10T1/2 cells

ABSTRACT: The two-stage cell transformation assay is an in vitro model cell culture system to identify the ability of chemicals to act as initiators or promoters of cell transforma- tion and also to study the cellular and molecular mechanisms of chemically induced morphological and neoplastic cell transformation. The global gene expression profiles of 3- methylcholanthrene (MCA)+12-O-tetradecanoylphorbol-13- acetate (TPA)-transformed C3H/10T1/2 cells are not known. Therefore, we have investigated the global transcriptional profile of MCA+TPA-transformed C3H10T1/2 cells using an 8M-CM-^W60 k probe microarray. The study revealed a differential regulation of pathways and gene expressions. Multifold dysregulation was seen in pathways of cancer, phagosomal activity, and tumor cell microenvironment information pro- cessing systems, notably the neuroactive ligandM-bM-^@M-^Sreceptor in- teraction, actin cytoskeleton regulation, tight junction, axon guidance, and cell adhesion molecules. The genes FGF1, EIF4E1B, MAGI1,and GRIA3 showed upregulation; these encoded the pluripotent fibroblast growth factor, the transla- tion initiation factor, the tight junction scaffolding protein, and the antiapoptotic as well as the enhancer of proliferation and migration, respectively. The genes CXCL7/CXCL5/CXCL12, H2DMB1,and HSPA1A showed downregulation; these encoded the chemotactic agent protein, the protein involved Total mRNA was isolated from the control as well as the MCA+TPA-transformed C3H/10T1/2 cells and complemen- tary RNA (cRNA) was prepared from mRNA (1 M-NM-

ORGANISM(S): Mus musculus

SUBMITTER: Dr Sushil Kumar

PROVIDER: E-GEOD-41142 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dysregulation of pathways involved in the processing of cancer and microenvironment information in MCA + TPA transformed C3H/10T1/2 cells.

Priya Shivam S Nigam Akanksha A Bajpai Preeti P Kumar Sushil S

In vitro cellular & developmental biology. Animal 20130322 4

The two-stage cell transformation assay is an in vitro model cell culture system to identify the ability of chemicals to act as initiators or promoters of cell transformation and also to study the cellular and molecular mechanisms of chemically induced morphological and neoplastic cell transformation. The global gene expression profiles of 3-methylcholanthrene (MCA) + 12-O-tetradecanoylphorbol-13-acetate (TPA)-transformed C3H/10T1/2 cells are not known. Therefore, we have investigated the global ...[more]

PMID: 23519560

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Project description:Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins can bind directly to AU-rich elements in mRNAs and promote transcript deadenylation and decay. The yeast Schizosaccharomyces pombe expresses a single TTP family member, Zfs1p, that has been linked to the mating response pathway and septum formation. We showed previously that Zfs1p can bind to and promote the destabilization of AU-rich element-containing transcripts. In this study, we identified additional target transcripts by comparing transcript levels in wild type and zfs1 mutant yeast, using deep sequencing and microarray approaches. We also used direct RNA sequencing to determine the locations of the polyA tails in both wild type and mutant strains, and to confirm the presence of potential Zfs1p target sequences within the mRNA. These studies identified a set of transcripts containing potential Zfs1p binding sites that accumulated significantly in the zfs1 mutants; a subset of these turned over more slowly in the zfs1 mutant strain, and bound directly to Zfs1p in co-immunoprecipitations. One apparent direct target encodes the transcription factor Cbf12p, which is known to increase cell-cell adhesion and flocculation when over-expressed. Studies of zfs1 and cbf12 double mutants demonstrated that the increased flocculation seen in zfs1 mutants is due, at least in part, to a direct effect on the turnover of cbf12 mRNA, leading in turn to changes in the levels of its transcriptionally regulated genes. These data suggest that Zfs1p can both directly and indirectly regulate the levels of transcripts involved in cell-cell adhesion in this species. Indicated strains were grown in YES media to approximately OD600=1.0 and total RNA was harvested, followed by polyA+ purification. Three independent microarrays were performed: 1) Project 488 included 3 biological replicates each of WT and zfs1M-bM-^HM-^F and compared PolyA+ RNA, 2) Project 529 included 5 biological replicates each of WT and zfs1M-bM-^HM-^F, and 3) Project 582 included 3 biological replicates each of WT, zfs1M-bM-^HM-^F, cbf12M-bM-^HM-^F, and zfs1M-bM-^HM-^Fcbf12M-bM-^HM-^F.

Dataset Information

Dysregulation of pathways involved in the processing of cancer and microenvironment information in MCA+TPA transformed C3H/10T1/2 cells

Publications

Dysregulation of pathways involved in the processing of cancer and microenvironment information in MCA + TPA transformed C3H/10T1/2 cells.

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