Noninvasive detection of lentiviral-mediated choline kinase targeting in a human breast cancer xe nog raft

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated phosphocholine (PC) and total choline (tCho) metabolites are widely established characteristics of most cancer cells, including breast cancer. Effective silencing of choline kinase (chk), the enzyme that converts choline to PC, is associated with reduced tumor growth. The functional importance and down-regulation of chk using RNA interference has been previously established. Here, we report on the preclinical evaluation of lentiviral vector-mediated downregulation of chk using short hairpin RNA (shRNA) in established tumors derived from human breast cancer cells. Concentrated lentivirus expressing shRNA against chk was injected i.v. in the tail vein of MDA-MB-231 tumor-bearing female severe combined immunodeficient mice. Transduction efficiency in cells and tumors in vivo was assessed optically by enhanced green fluorescent protein expression and additionally from chk mRNA and protein levels. An 80% reduction in chk mRNA and protein was achieved following ∼ 90% transduction efficiency in cells. After transduction with chkshRNA, 1H magnetic resonance spectroscopy (MRS) of cell and tumor extracts showed decreases in PC and tCho levels (P<0.01 and 0.05, respectively) in comparison with controls. PC levels were monitored noninvasively by 31> P MRS in tumors and by 1H MBS in cell and tumor tissue extracts. Noninvasive P MB spectra of chk-shRNA-transduced tumors in vivo showed lower PC and phosphomonoester levels that were associated with reduced tumor growth and proliferation. This study shows the use of lentiviral vectors to target chk in a human breast cancer xenograft and noninvasive MRS detection of this targeting

Original languageEnglish (US)
Pages (from-to)3464-3471
Number of pages8
JournalCancer Research
Volume69
Issue number8
DOIs
StatePublished - Apr 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Noninvasive detection of lentiviral-mediated choline kinase targeting in a human breast cancer xe nog raft'. Together they form a unique fingerprint.

Cite this