The flt-1 promoter for transcriptional targeting of teratocarcinoma

Cancer Res. 2002 Mar 1;62(5):1271-4.

Abstract

Flt-1, a receptor for vascular endothelial growth factor, is known to display dysregulated expression in both tumor vasculature and tumor cells per se, suggesting that the flt-1 promoter might be a useful candidate to achieve tumor-specific transgene expression. In addition, adenoviral vectors containing transgenes under the control of the flt-1 promoter achieve very low levels of expression in the normal liver, the major organ responsible for blood clearance of adenoviruses and inadvertent transgene-related toxicity. Thus, we assessed the ability of adenoviral vectors containing the flt-1 promoter to achieve transgene expression in a range of gynecological and breast tumor lines. High transgene expression levels were detected in teratocarcinoma lines, correlating with levels of flt-1 mRNA. These results suggest that the flt-1 promoter could be useful for transcriptionally targeted gene expression to teratocarcinoma, and that evaluation in other flt-1-positive tumors is warranted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Therapy*
  • Humans
  • Mice
  • Myosin Heavy Chains
  • Nonmuscle Myosin Type IIB
  • Promoter Regions, Genetic*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Teratocarcinoma / therapy*
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1

Substances

  • Extracellular Matrix Proteins
  • RNA, Messenger
  • FLT1 protein, human
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains