Modulation by bexarotene of mRNA expression of genes in mouse lung tumors.
Bexarotene has demonstrated chemopreventive and therapeutic efficacy towards mouse lung tumors. Using specimens from our published study that demonstrated the efficacy of bexarotene, we report herein its ability to modulate mRNA expression of genes in both lung and lung tumors. Strain A/J mice were administered vinyl carbamate to induce lung tumors. This was followed by 200 mg/kg body weight of bexarotene administered by oral gavage during Wks 4-25 or 23-25. The mice were sacrificed at Wk 25. The expression of 26 genes was decreased in lung tumors, whereas only two genes, Apolipoprotein D and CYP26b, had their mRNA expression increased by bexarotene. Genes with increased mRNA expression in untreated lung tumors include: epiregulin and kininogen-1 (increased by more than 40-fold) and Caspase-3, Cyclin D1, DNA methyltransferase 3a (Dnmt-3a), E-prostanoid 3 receptor (EP3), c-myc, surfactant protein-C, and survivin (increased by 1.7- to 3.6-fold). Bexarotene decreased the mRNA expression of Caspase-3, Dnmt-3a, EP3, and survivin, as well as the expression of the Cyclin E1, estrogen receptor-alpha, and iNOS genes. Bexarotene had a greater effect in decreasing the expression of Caspase-3, Cyclin E1, Dnmt-3a, EP3, iNOS, and survivin, when administered to mice with established tumors than when administered to mice while tumors were emerging. In summary, bexarotene modulated mRNA expression of genes in mouse lung tumors, being more effective in established tumors than in emerging tumors, suggesting that modulation of expression could be useful as a biomarker for the therapeutic and chemopreventive activity of the drug, especially in established tumors.
Alyaqoub
Fadel S
FS
Department of Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, Ohio, USA.
Liu
Yue
Y
Tao
Lianhui
L
Steele
Vernon E
VE
Lubet
Ronald A
RA
Pereira
Michael A
MA
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000378:metabolism*; D000077610:Bexarotene; D000090205:DNA Methyltransferase 3A; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D010455:Peptides / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects; D014520:Urethane / Q000031:analogs & derivatives / Q000633:toxicity; D014598:Uteroglobin / Q000378:metabolism
D016588:Anticarcinogenic Agents; C000715535:Dnmt3a protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; C556390:Scgb1a1 protein, mouse; C489680:Sftpc protein, mouse; D013764:Tetrahydronaphthalenes; D014520:Urethane; C017963:vinyl carbamate; D014598:Uteroglobin; D000077610:Bexarotene; D000090205:DNA Methyltransferase 3A