Enhanced invasive properties of rat embryo fibroblasts transformed by adenovirus E1A mutants with deletions in the carboxy-terminal exon.
E1A genes deficient in the carboxy-terminal exon can cooperate with activated ras oncogenes to induce transformation of rat embryo fibroblasts. However, the resulting transformed foci show a distinct appearance characterized by a decreased adhesion of the cells to the substrate. Here, we demonstrate that cell lines derived from foci showing the variant morphology are defective in down-regulation of stromelysin 1 metalloprotease expression and show an increased invasive propensity compared with cells transformed by wild-type E1A. The altered focus morphology, the high invasive propensity and the elevated stromelysin 1 expression were abrogated by glucocorticoid treatment. Our results show that E1A functions necessary for transformation and inhibition of invasive properties may be separated, and indicate that a 23 amino acid serine/threonine-rich region within the E1A carboxy-terminal exon is required for efficient repression of metalloprotease expression in transformed cells.
Linder
S
S
Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden.
Popowicz
P
P
Svensson
C
C
Marshall
H
H
Bondesson
M
M
Akusjärvi
G
G
D017456:Adenovirus Early Proteins; D000818:Animals; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015870:Gene Expression; D066298:In Vitro Techniques; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3