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PMID: 10428026 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis.

Cell ·Vol. 98 ·No. 2 ·1999-07-23 ·Pages 137-46

Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier JP, Gray JW, Pinkel D, Bissell MJ, Werb Z

Abstract

Matrix metalloproteinases (MMPs) are invariably upregulated in the stromal compartment of epithelial cancers and appear to promote invasion and metastasis. Here we report that phenotypically normal mammary epithelial cells with tetracycline-regulated expression of MMP3/stromelysin-1 (Str1) form epithelial glandular structures in vivo without Str1 but form invasive mesenchymal-like tumors with Str1. Once initiated, the tumors become independent of continued Str1 expression. Str1 also promotes spontaneous premalignant changes and malignant conversion in mammary glands of transgenic mice. These changes are blocked by coexpression of a TIMP1 transgene. The premalignant and malignant lesions have stereotyped genomic changes unlike those seen in other murine mammary cancer models. These data indicate that Str1 influences tumor initiation and alters neoplastic risk.

MeSH Terms
Animals Antineoplastic Agents/pharmacology Carcinogenicity Tests Cell Differentiation/drug effects,physiology Cells, Cultured Epithelial Cells/chemistry,cytology,metabolism Female Fibrosis Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genome Humans Hyperplasia Keratins/analysis Mammary Neoplasms, Experimental/metabolism,pathology Matrix Metalloproteinase 3/genetics,metabolism Mesoderm/cytology Mice Mice, SCID Mice, Transgenic Pregnancy Stromal Cells/cytology,enzymology Tissue Inhibitor of Metalloproteinase-1/pharmacology Vimentin/analysis
Chemicals
Antineoplastic Agents Tissue Inhibitor of Metalloproteinase-1 Vimentin Keratins Matrix Metalloproteinase 3
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sternlicht M D
Department of Anatomy, University of California, San Francisco 94143-0452, USA. [email protected]
Lochter A
Sympson C J
Huey B
Rougier J P
Gray J W
Pinkel D
Bissell M J
Werb Z
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/s0092-8674(00)81009-0
Email
[email protected]
Published
1999-07-23
Pages
137-46
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2853255
Subset
IM
Grants
NCI NIH HHS · R37 CA064786 · United States
NCI NIH HHS · P01 CA072006-020003 · United States
NCI NIH HHS · CA72006 · United States
NCI NIH HHS · R01 CA057621 · United States
NCI NIH HHS · CA64786 · United States
NCI NIH HHS · P01 CA072006 · United States
NCI NIH HHS · CA57621 · United States
NCI NIH HHS · R01 CA064786-04A1 · United States
NCI NIH HHS · R01 CA057621-07 · United States
NCI NIH HHS · R01 CA064786 · United States
External Links
PubMed source DOI: 10.1016/s0092-8674(00)81009-0 PMC Full Text View journal details
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