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

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• 作者：Martin C Abba (1) (4)
  Yuhui Hu (1)
  Carla C Levy (1)
  Sally Gaddis (1)
  Frances S Kittrell (2)
  Yun Zhang (2)
  Jamal Hill (2)
  Reid P Bissonnette (3)
  Daniel Medina (2)
  Powel H Brown (2)
  C Marcelo Aldaz (1)
  
• 刊名：BMC Medical Genomics
• 出版年：2008
• 出版时间：December 2008
• 年：2008
• 卷：1
• 期：1
• 全文大小：3476KB
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  53. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1755-8794/1/40/prepub
  
• 作者单位：Martin C Abba (1) (4)
  Yuhui Hu (1)
  Carla C Levy (1)
  Sally Gaddis (1)
  Frances S Kittrell (2)
  Yun Zhang (2)
  Jamal Hill (2)
  Reid P Bissonnette (3)
  Daniel Medina (2)
  Powel H Brown (2)
  C Marcelo Aldaz (1)
  
  1. Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, TX, USA
  4. CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
  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
  
• ISSN：1755-8794

文摘

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.