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

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 transformatio...

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Bibliographic Details
Published in:In vitro cellular & developmental biology. Animal 2013-04, Vol.49 (4), p.295-305
Main Authors: Priya, Shivam, Nigam, Akanksha, Bajpai, Preeti, Kumar, Sushil
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Animals
antigens
apoptosis
Biomedical and Life Sciences
Carcinogenesis
carcinogenicity
Carcinogens - toxicity
cell adhesion
Cell Biology
Cell Culture
Cell culture techniques
Cell growth
Cell Line, Transformed
cell transformation assay
Cell Transformation, Neoplastic - chemically induced
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
chemotaxis
Developmental Biology
Down regulation
Embryonic cells
fibroblasts
Gene expression
gene expression regulation
genes
in vitro studies
Life Sciences
mechanism of action
Methylcholanthrene - toxicity
Mice
microarray technology
microfilaments
Neoplastic cell transformation
phenotype
scaffolding proteins
Signal Transduction
Stem Cells
Tetradecanoylphorbol Acetate - toxicity
tight junctions
TOXICOLOGY/CHEMICAL CARCINOGENESIS
transcription (genetics)
Transformed cell line
translation (genetics)
Tumor Microenvironment
Tumors
Up regulation
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Summary: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 transcriptional profile of MCA + TPA-transformed C3H10T1/2 cells using an 8 × 60 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 processing systems, notably the neuroactive ligand–receptor interaction, 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 translation 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 in MHC class II antigen processing/presentation or participating in cell adhesion/phagosomal activity/autoimmune disorder, and the chaperone protein stabilizing the existing as well as newly translated cytosolic/organelle proteins against aggregation, respectively. By loss or gain of function, these dysregulated genes apparently seem to reprogram cells for apoptosis or proliferation and support their transformation into the tumor cell phenotype. The observed molecular changes can be seen as molecular signatures of transformed cells and can be of use as objective evidences to C3H/10T1/2 cell transformation assay in investigations on the carcinogenic potential of chemicals and their mechanism of actions using in vitro carcinogenesis method.
ISSN:1071-2690
1543-706X
DOI:10.1007/s11626-013-9593-5