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         headline:Estrogen and insulin-like growth factor-I (IGF-I) independently down-regulate critical repressors of breast cancer growth
         description:Although estrogen receptor alpha (ERα) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3 or 24 h. IGF-I regulated mRNA of five to tenfold more genes than E2, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors, for example, B-cell linker (BLNK), were down-regulated by IGF-I and E2. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ERα. However, repression by IGF-I or E2 required common kinases, such as PI3K and MEK, suggesting downstream convergence of the two pathways. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and, for some genes, the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ERα and IGF-IR signaling may require co-targeting of both pathways.
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            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
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      name:Simeen Malik
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:ZaWaunyka Lazard
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Isere Kuiatse
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Hee-Tae Kim
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Anna Tsimelzon
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Chad J. Creighton
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Susan G. Hilsenbeck
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Powell H. Brown
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Steffi Oesterreich
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
      name:Adrian V. Lee
      affiliation:
            name:Baylor College of Medicine
            address:
               name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:Baylor College of Medicine
            address:
               name:Department of Medicine, Baylor College of Medicine, Houston, USA
               type:PostalAddress
            type:Organization
            name:University of Pittsburgh Cancer Institute, Magee Women’s Research Institute
            address:
               name:Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Magee Women’s Research Institute, Pittsburgh, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA
      name:Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
      name:Department of Medicine, Baylor College of Medicine, Houston, USA
      name:Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Magee Women’s Research Institute, Pittsburgh, USA
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