Association of nuclear localization of a long interspersed nuclear element-1 protein in breast tumors with poor prognostic outcomes

Chris R. Harris, Robin Normart, Qifeng Yang, Elizabeth Stevenson, Bruce G. Haffty, Shridar Ganesan, Carlos Cordon-Cardo, Arnold J. Levine, Laura H. Tang

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Within healthy human somatic cells, retrotransposition by long interspersed nuclear element-1 (also known as LINE-1 or L1) is thought to be held in check by a variety of mechanisms, including DNA methylation and RNAi. The expression of L1-ORF1 protein, which is rarely found in normal tissue, was assayed using antibodies with a variety of clinical cancer specimens and cancer cell lines. L1-ORF1p expression was detected in nearly all breast tumors that the authors examined, and the protein was also present in a high percentage of ileal carcinoids, bladder, and pancreatic neuroendocrine tumors, as well as in a smaller percentage of prostate and colorectal tumors. Tumors generally demonstrated cytoplasmic L1-ORF1p; however, in several breast cancers, L1-ORF1p was nuclear. Patients with breast tumors displaying nuclear L1-ORF1p had a greater incidence of both local recurrence and distal metastases and also showed poorer overall survival when compared with patients with tumors displaying cytoplasmic L1-ORF1p. These data suggest that expression of L1-ORF1p is widespread in many cancers and that redistribution from cytoplasm to nucleus could be a poor prognostic indicator during breast cancer. High expression and nuclear localization of L1-ORF1p may result in a higher rate of L1 retrotransposition, which could increase genomic instability.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalGenes and Cancer
Volume1
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Breast cancers
  • Line expression
  • Line movement

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