Tumorigenic and metastatic properties of two ras-oncogene transfected rat fibrosarcoma cell lines defective in c-jun

Oncogene. 1994 Dec;9(12):3655-63.

Abstract

We here report the spontaneous loss of both homologues of the c-jun gene in two cell lines, isolated after transfection of rat embryo fibroblasts with single ras-oncogenes. These cells lines (designated A14 and B25) grow rapidly in vitro, have transformed morphologies and are invasive through reconstituted basal membranes. Both c-jun defective cell lines were found to be tumorigenic and metastatic in athymic mice. Loss of c-jun was paralleled by a dramatic decrease in interstitial collagenase expression, whereas stromelysin mRNA expression in c-jun- A14 and B25 cells was similar to that observed in c-jun+ transformed cell lines. Transient transfection experiments using reporter plasmids showed that stromelysin promoter activity in A14 cells was severely impaired by a point mutation in the -71 to -65 AP-1 motif, and was inhibited by a Jun dominant negative mutant. Gel mobility shift studies demonstrated the presence of a factor in A14 nuclear extracts capable of binding the stromelysin TRE. This factor bound JunB, JunD and Fos antibodies. Our findings suggest that c-Jun is not required for the tumorigenic and metastatic potential of ras-transformed fibrosarcoma cells, and that AP-1 protein(s) lacking c-Jun are capable of activating the stromelysin gene promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Collagenases / genetics
  • Fibrosarcoma / genetics*
  • Genes, jun*
  • Genes, ras*
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases / genetics
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / genetics*
  • Neoplasms, Experimental / etiology
  • Osteopontin
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Sialoglycoproteins / genetics
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Spp1 protein, rat
  • Transcription Factor AP-1
  • Osteopontin
  • Collagenases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3