Linking transcriptional elongation and messenger RNA export to metastatic breast cancers

Shanchun Guo, Mohamed Ali Hakimi, David Baillat, Xiaowei Chen, Michele J. Farber, Andres J P Klein-Szanto, Neil S. Cooch, Andrew K. Godwin, Ramin Shiekhattar

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38 Scopus citations

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 hTKEX84 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.

Original languageEnglish (US)
Pages (from-to)3011-3016
Number of pages6
JournalCancer Research
Volume65
Issue number8
StatePublished - Apr 15 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Guo, S., Hakimi, M. A., Baillat, D., Chen, X., Farber, M. J., Klein-Szanto, A. J. P., Cooch, N. S., Godwin, A. K., & Shiekhattar, R. (2005). Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Research, 65(8), 3011-3016.