SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells

Authors

  • Jessica A. Thornley,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Biology and Biochemistry, University of Bath, Bath, UK
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  • Heidi W. Trask,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Carol S. Ringelberg,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Genetics, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Christian J.A. Ridley,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Biology and Biochemistry, University of Bath, Bath, UK
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  • Sinny Wang,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Richard Cowper Sal-Lari,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Genetics, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Jason H. Moore,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Genetics, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Murray Korc,

    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    3. Department of Pharmacology and Toxicology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
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  • Craig R. Tomlinson

    Corresponding author
    1. Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    2. Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    3. Department of Pharmacology and Toxicology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
    • Department of Medicine, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756.
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Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the United States because most patients are diagnosed too late in the course of the disease to be treated effectively. Thus, there is a pressing need to more clearly understand how gene expression is regulated in cancer cells and to identify new biomarkers and therapeutic targets. Translational regulation is thought to occur primarily through non-SMAD directed signaling pathways. We tested the hypothesis that SMAD4-dependent signaling does play a role in the regulation of mRNA entry into polysomes and that novel candidate genes in pancreatic cancer could be identified using polysome RNA from the human pancreatic cancer cell line BxPC3 with or without a functional SMAD4 gene. We found that (i) differentially expressed whole cell and cytoplasm RNA levels are both poor predictors of polysome RNA levels; (ii) for a majority of RNAs, differential RNA levels are regulated independently in the nucleus, cytoplasm, and polysomes; (iii) for most of the remaining polysome RNA, levels are regulated via a “tagging” of the RNAs in the nucleus for rapid entry into the polysomes; (iv) a SMAD4-dependent pathway appears to indeed play a role in regulating mRNA entry into polysomes; and (v) a gene list derived from differentially expressed polysome RNA in BxPC3 cells generated new candidate genes and cell pathways potentially related to pancreatic cancer. © 2011 Wiley Periodicals, Inc.

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