Microarray analysis of altered gene expression in murine fibroblasts transformed by nickel(II) to nickel(II)-resistant malignant phenotype.
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.
Kowara
Renata
R
Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702, USA. Renata.Kowara@nrc-cnrc.gc.ca
Karaczyn
Aldona
A
Cheng
Robert Y S
RY
Salnikow
Konstantin
K
Kasprzak
Kazimierz S
KS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D019940:Genes, bcl-1 / Q000187:drug effects / Q000502:physiology; D018816:Genes, cdc / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D005981:Glutathione Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis / Q000379:methods* / Q000639:trends; D009532:Nickel / Q000009:adverse effects*; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D035165:Transcription Factors, General / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D003598:Cytoskeletal Proteins; D006133:Growth Substances; D007527:Isoenzymes; D008565:Membrane Proteins; D015534:Trans-Activators; D035165:Transcription Factors, General; D051176:beta Catenin; D009532:Nickel; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D005982:Glutathione Transferase; D005981:Glutathione Synthase; D005978:Glutathione