Suppression of prostate carcinoma cell invasion by expression of antisense L-plastin gene

Am J Pathol. 1999 Jul;155(1):115-22. doi: 10.1016/S0002-9440(10)65106-1.


Based on the finding that gene expression for the actin-bundling protein L-plastin is inducible by androgen and that L-plastin is overexpressed in malignant epithelium of the prostate, we examined the functional consequences of L-plastin down-regulation in prostate carcinoma cell lines by both transfection and retroviral infection. We constructed retroviral vectors to express two different regions of the L-plastin gene, a 1713-bp 3'-coding portion and a 163-bp 5'-untranslated region, both in antisense orientation. Introduction of either constructs into prostate carcinoma cell lines, PC-3 and its isogenic but metastatic variant PC-3M cells, reduced the growth rates of both cell lines. In vitro invasion and motility of PC-3 and PC-3M cells were drastically suppressed (approximately 10-fold) by the expression of the antisense constructs. Evidence was obtained to indicate that L-plastin protein levels were indeed decreased by the antisense expression. The antisense construct for the 5'-untranslated region with the most unique sequence for the L-plastin gene was more effective in down-regulation efficiency compared with the larger antisense construct in the coding region, which maintains homology to other members of the plastin gene family. Cells infected with the 163-bp antisense virus, which were also tested in a nude mouse diaphragm invasion model, showed suppression of in vivo invasion of both PC-3 and PC-3M cells. These results suggested that overexpression of L-plastin might be functionally involved in prostate cancer invasion and metastasis, and raised the possibility that L-plastin gene-specific antisense delivery could potentially be a useful approach to interfere with prostate cancer progression in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / genetics*
  • Antisense Elements (Genetics) / pharmacology*
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Nude
  • Microfilament Proteins
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*


  • Antisense Elements (Genetics)
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Phosphoproteins
  • plastin