Microarray analysis of altered gene expression in murine fibroblasts transformed by nickel(II) to nickel(II)-resistant malignant phenotype
- Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States)
B200 cells are Ni(II)-transformed mouse BALB/c-3T3 fibroblasts displaying a malignant phenotype and increased resistance to Ni(II) toxicity. In an attempt to find genes whose expression has been altered by the transformation, the Atlas Mouse Stress/Toxicology cDNA Expression Array (Clontech Laboratories, Inc., Palo Alto, CA) was used to analyze the levels of gene expression in both parental and Ni(II)-transformed cells. Comparison of the results revealed a significant up- or downregulation of the expression of 62 of the 588 genes present in the array (approximately 10.5%) in B200 cells. These genes were assigned to different functional groups, including transcription factors and oncogenes (9/14; fractions in parentheses denote the number of up-regulated versus the total number of genes assigned to this group), stress and DNA damage response genes (11/12), growth factors and hormone receptors (6/9), metabolism (7/7), cell adhesion (2/7), cell cycle (3/6), apoptosis (3/4), and cell proliferation (2/3). Among those genes, overexpression of beta-catenin and its downstream targets c-myc and cyclin D1, together with upregulated cyclin G, points at the malignant character of B200 cells. While the increased expression of glutathione (GSH) synthetase, glutathione-S-transferase A4 (GSTA4), and glutathione-S-transferase theta (GSTT), together with high level of several genes responding to oxidative stress, suggests the enforcement of antioxidant defenses in Ni-transformed cells.
- OSTI ID:
- 20721801
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 205, Issue 1; Other Information: DOI: 10.1016/j.taap.2004.10.006; PII: S0041-008X(04)00475-2; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANOXIA
ANTIOXIDANTS
APOPTOSIS
BIOLOGICAL STRESS
CELL CYCLE
CELL PROLIFERATION
DNA DAMAGES
FIBROBLASTS
GLUTATHIONE
GROWTH FACTORS
INSULIN
LIGASES
METABOLISM
MICE
NICKEL
ONCOGENES
OXYGEN
PHENOTYPE
POLYMERASE CHAIN REACTION
RECEPTORS
TOXICITY
TRANSCRIPTION
TRANSCRIPTION FACTORS