Transcriptomic signature of Bexarotene (Rexinoid LGD1069) on mammary gland from three transgenic mouse mammary cancer models.

ABBA MC; HU Y; LEVY CC; GADDIS S; KITTRELL FS; ZHANG Y; HILL J; BISSONNETTE RP; MEDINA D; BROWN PH; ALDAZ CM

BMC Medical Genomics

Biomed Central

Lugar: Londres; Año: 2008 p. 1 - 13

1755-8794

Background: The rexinoid bexarotene (LGD1069, Targretin) is a highly selective retinoid ×receptor (RXR) agonist that inhibits the growth of pre-malignant and malignant breast cells.Bexarotene was shown to suppress the development of breast cancer in transgenic mice modelswithout side effects. The chemopreventive effects of bexarotene are due to transcriptionalmodulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was toobtain a profile of the genes modulated by bexarotene on mammary gland from three transgenicmouse mammary cancer models in an effort to elucidate its molecular mechanism of action and forthe identification of biomarkers of effectiveness.Methods: Serial analysis of gene expression (SAGE) was employed to profile the transcriptome of p53-null, MMTV-ErbB2, and C3(1)-SV40 mammary cells obtained from mice treated withbexarotene and their corresponding controls.Results: This resulted in a dataset of approximately 360,000 transcript tags representing over20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changesinduced by bexarotene in mammary gland revealed that 89 genes were dysregulated among thethree transgenic mouse mammary models. From these, 9 genes were common to the three modelsstudied.Conclusion: Analysis of the indicated core of transcripts and protein-protein interactions of thiscommonly modulated genes indicate two functional modules significantly affected by rexinoidbexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targetingof cancer-causing genes related with cell proliferation, differentiation and apoptosis.