title: Linking transcriptional elongation and messenger RNA export to metastatic breast cancers.
abstract: The biochemical pathways that are disrupted in the genesis of sporadic breast cancers remain unclear. Moreover, the present prognosticating markers used to determine the prognosis of node-negative patient leads to probabilistic results, and the eventual clinical course is far from certain. Here we identified the human TREX complex, a multiprotein complex that links transcription elongation to mRNA transport, as culprit of aggressive human breast cancers. We show that whereas p84N5 (called hTREX84) is expressed at very low levels in normal breast epithelial cells, it is highly expressed in breast tumors. Importantly, hTREX84 expression correlates with tumor size and the metastatic state of the tumor progression. Reduction of hTREX84 levels in breast cancer cell lines by small interfering RNA result in inhibition of cellular proliferation and abrogation of mRNA export. These results not only identify hTREX84 as a prognosticator of breast cancer but also delineate human TREX complex as a target for therapeutic drugs against breast cancer.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center and Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Shanchun
authors.initials: S
authors.lastname: Guo
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.forename: David
authors.initials: D
authors.lastname: Baillat
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.forename: Michele J
authors.initials: MJ
authors.lastname: Farber
authors.forename: Andres J P
authors.initials: AJ
authors.lastname: Klein-Szanto
authors.forename: Neil S
authors.initials: NS
authors.lastname: Cooch
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D018450:Disease Progression; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D035602:Transcriptional Elongation Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C400546:THOC1 protein, human; D035602:Transcriptional Elongation Factors