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.