INVESTIGADORES
SREBROW Anabella
artículos
Título:
Misregulation of stromelysin-1 expression in mouse mammary tumor cells accompanies acquisition of stromelysin-1-dependent invasive properties.
Autor/es:
LOCHTER A; SREBROW A; SYMPSON CJ; TERRACIO N; WERB Z; BISSELL M J
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 1997 vol. 272 p. 5007 - 5015
ISSN:
0021-9258
Resumen:
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Stromelysin-1
is a member of the metalloproteinase family of extracellular matrix-degrading
enzymes that regulates tissue remodeling. We previously established a transgenic
mouse model in which rat stromelysin-1 targeted to the mammary gland augmented
expression of endogenous stromelysin-1, disrupted functional differentiation,
and induced mammary tumors. A cell line generated from an adenocarcinoma in one
of these animals and a previously described mammary tumor cell line generated
in culture readily invaded both a reconstituted basement membrane and type I
collagen gels, whereas a nonmalignant, functionally normal epithelial cell line
did not. Invasion of Matrigel by tumor cells was largely abolished by
metalloproteinase inhibitors, but not by inhibitors of other proteinase
families. Inhibition experiments with antisense oligodeoxynucleotides revealed
that Matrigel invasion of both cell lines was critically dependent on
stromelysin-1 expression. Invasion of collagen, on the other hand, was reduced
by only 40-50%. Stromelysin-1 was expressed in both malignant and nonmalignant
cells grown on plastic substrata. Its expression was completely inhibited in
nonmalignant cells, but up-regulated in tumor cells, in response to Matrigel.
Thus misregulation of stromelysin-1 expression appears to be an important
aspect of mammary tumor cell progression to an invasive phenotype.