The aryl hydrocarbon receptor agonist 3,3',4,4',5-pentachlorobiphenyl induces distinct patterns of gene expression between hepatoma and glioma cells: chromatin remodeling as a mechanism for selective effects.
Genome-wide oligonucleotide DNA microarrays and real time RT-PCR were used to assess differential gene expression in rat glioma and hepatoma cell lines after exposure to the aryl hydrocarbon receptor (AhR) agonist 3,3',4,4',5-pentachlorobiphenyl (penta-CB). Under maximal inducing concentrations for cytochrome P450 1A1 (CYP1A1) in H4IIE rat hepatoma cells, both H4IIE and C6 rat glioma cells were exposed to sub-micromolar concentrations of penta-CB for 24h. Differential gene expression for approximately 28,000 gene probes were computationally analyzed and compared. As expected, penta-CB potently activated CYP1A1/2 transcription in liver-derived H4IIE hepatoma cells yet did not do so in brain-derived C6 glioma cells. Additionally, we show that penta-CB causes: (1) distinct patterns of gene expression between tumor cells derived from liver or brain; (2) robust transcriptional activation of select C6 glioma gene ontologies; (3) over-expression of H4IIE hepatoma genes associated with tumor progression in liver; (4) greater than 100-fold over-expression of C6 glioma genes associated with protein processing and programmed cell death and/or metastasis; (5) tissue-selective histone deacetylase inhibition in C6 glioma, but not H4IIE hepatoma cells as signaled by galectin-1 over-expression.
Maier
Mark S V
MS
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523-1680, USA.
Legare
Marie E
ME
Hanneman
William H
WH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects* / Q000648:ultrastructure; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037483:Galectin 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D008024:Ligands; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects
D002843:Chromatin; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D037483:Galectin 1; D056572:Histone Deacetylase Inhibitors; D008024:Ligands; D012334:RNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl