Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents.
Identification of specific etiological carcinogens is one of the most important issues in environmental-toxicology studies. In this study, cDNA microarrays were used to analyze gene expression and discern chemical-associated profiles induced by a variety of tumor promoting agents in transformed cells. Two-stage transformation model of BALB/c 3T3 cells was established with MNNG as initiator, and 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid (OA), or cadmium chloride (CdCl(2)) as tumor promoters. Nine morphologically transformed foci were isolated and the anchorage-independent growth of transformed cells was verified. The gene expression alterations in foci were evaluated using cDNA microarray with 1796 mouse genes. Unsupervised hierarchical clustering analysis revealed that the nine foci were classified into three groups in concordance with the promoters used to induce them and characteristic clusters of genes were identified. In these clusters, genes associated with oxidative stress were specially upregulated following distinct promoter exposure. Moreover, common gene expression alterations were also observed in foci, including upregulated genes associated with cell proliferation and downregulated genes associated with extracellular matrix. Our results demonstrate the presence of unique gene expression profiles in transformed cells which reflect the etiological chemicals and indicate the importance of characteristic molecular alterations as potential biomarkers of exposure to tumor promoters.
Department of Hygiene Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
Lin
L
Ao
Jin-Yi
JY
Liu
Wen-Bin
WB
Liu
Li-Hong
LH
Gao
Ran
R
Hu
Zhi-Jun
ZJ
Fang
Zhi-Xiong
ZX
Zhen
Ming-Hui
MH
Huang
Meng-Su
MS
Yang
Jia
J
Cao
D000818:Animals; D041702:BALB 3T3 Cells; D019256:Cadmium Chloride / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D019319:Okadaic Acid / Q000633:toxicity*; D040081:Protein Array Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D002273:Carcinogens; D019319:Okadaic Acid; D019256:Cadmium Chloride; D013755:Tetradecanoylphorbol Acetate