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PMID: 10713697 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Review

The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter.

Oncogene ·Vol. 19 ·No. 8 ·2000-02-21 ·Pages 1102-13

Sternlicht MD, Bissell MJ, Werb Z

Abstract

Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably upregulated in epithelial cancers and are key agonists in angiogenesis, invasion and metastasis. Yet most MMPs are secreted not by the cancer cells themselves, but by stromal cells within and around the tumor mass. Because the stromal environment can influence tumor formation, and because MMPs can alter this environment, MMPs may also contribute to the initial stages of cancer development. Several recent studies in MMP-overexpressing and MMP-deficient mice support this possibility, but have required carcinogens or pre-existing oncogenic mutations to initiate tumorigenesis. Here we review the spontaneous development of premalignant and malignant lesions in the mammary glands of transgenic mice that express an autoactivating form of MMP-3/stromelysin-1 under the control of the whey acidic protein gene promoter. These changes were absent in nontransgenic littermates and were quenched by co-expression of a human tissue inhibitor of metalloproteinases-1 (TIMP-1) transgene. Thus by altering the cellular microenvironment, stromelysin-1 can act as a natural tumor promoter and enhance cancer susceptibility.

MeSH Terms
Animals Female Humans Mammary Neoplasms, Experimental/enzymology,genetics Matrix Metalloproteinase 3/genetics,metabolism Matrix Metalloproteinases/genetics,metabolism Mice Mice, Transgenic Tissue Inhibitor of Metalloproteinase-1/genetics,metabolism Tissue Inhibitor of Metalloproteinase-2/genetics,metabolism
Chemicals
Tissue Inhibitor of Metalloproteinase-1 Tissue Inhibitor of Metalloproteinase-2 Matrix Metalloproteinases Matrix Metalloproteinase 3
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sternlicht M D
Department of Anatomy, University of California, 513 Parnassus Avenue, HSW-1301, San Francisco, California, CA 94143-0452, USA.
Bissell M J
Werb Z
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
0950-9232
DOI
10.1038/sj.onc.1203347
Published
2000-02-21
Pages
1102-13
Language
English
Region
England
NLM ID
8711562
PMCID
PMC2933206
Subset
IM
Grants
NCI NIH HHS · P01 CA072006-07 · United States
NCI NIH HHS · CA72006 · United States
NCI NIH HHS · R01 CA057621 · United States
NCI NIH HHS · P01 CA072006 · United States
NCI NIH HHS · CA57621 · United States
NCI NIH HHS · R01 CA057621-07 · United States
External Links
PubMed source DOI: 10.1038/sj.onc.1203347 PMC Full Text View journal details
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