title: SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells.
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.
authors.affiliation: Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Thornley
authors.forename: Heidi W
authors.initials: HW
authors.lastname: Trask
authors.forename: Carol S
authors.initials: CS
authors.lastname: Ringelberg
authors.forename: Christian J A
authors.initials: CJ
authors.lastname: Ridley
authors.forename: Sinny
authors.initials: S
authors.lastname: Wang
authors.forename: Richard Cowper
authors.initials: RC
authors.lastname: Sal-Lari
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Craig R
authors.initials: CR
authors.lastname: Tomlinson
mesh_terms: D002467:Cell Nucleus / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D012313:RNA