Research article

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

Martin C Abba^1,4 , Yuhui Hu¹ , Carla C Levy¹ , Sally Gaddis¹ , Frances S Kittrell² , Yun Zhang² , Jamal Hill² , Reid P Bissonnette³ , Daniel Medina² , Powel H Brown² and C Marcelo Aldaz¹

¹  Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, TX, USA

²  Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, 77030, TX, USA

³  Department of Molecular Oncology, Ligand Pharmaceuticals Inc., San Diego, California, 92121, USA

⁴  CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina

author email corresponding author email

BMC Medical Genomics 2008, 1:40doi:10.1186/1755-8794-1-40

Published:	11 September 2008

Abstract

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 models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the 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 with bexarotene and their corresponding controls.

Results

This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied.

Conclusion

Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.