Accession Number : ADA332160

Title :   Function of the Stroma-Derived Metalloproteinase, Stromelysin-3, in Invasive Breast Carcinomas

Descriptive Note : Annual rept. 27 Jun 96-26 Jun 97

Corporate Author : MICHIGAN UNIV ANN ARBOR

Personal Author(s) : Weiss, Stephen J.

PDF Url : ADA332160

Report Date : JUL 1997

Pagination or Media Count : 22

Abstract : Stromelysin-3 (ST-3), a member of the matrix metalloproteinase (MMP) family, is expressed in stromal cells surrounding invasive breast carcinoma cells where it undergoes processing to its active form by an intracellular, proprotein convertase-dependent pathway. While strong correlations between disease progression and ST-3 expression suggest that the proteinase plays a critical role in breast cancer, human ST-3 is the only matrix metalloproteinase that does not express a marked ability to degrade components of the extracellular matrix (ECM). To further characterize the role of ST-3 in vivo, our attention focused on the analysis of lines of transgenic mice wherein the whey acidic protein (WAP) gene was used to direct human ST-3 expression to mammary tissue during late pregnancy through lactation. In these studies, high levels of the ST-3 transgene were generated in vivo which unexpectedly triggered a massive involution program. Surprisingly, ST-3 not only induced an apoptotic program, but also initiated changes in the underlying basement membrane in vivo. In addition, ST-3 expression also appeared to induce an exaggerated angiogenic response in involuting tissues. These data provide the first evidence that ST-3 can regulate mammary epithelial-ECM interactions and angiogenesis vivo.

Descriptors :   *IN VIVO ANALYSIS, *MAMMARY GLANDS, *PROTEINS(CONJUGATED), *BREAST CANCER, CELLS, NEOPLASMS, CELLS(BIOLOGY).

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE