Accession Number : ADA336736

Title :   Growth Factors and Metalloproteinases in Breast Cancer Development and Progression.

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : VANDERBILT UNIV NASHVILLE TN SCHOOL OFMEDICINE

Personal Author(s) : Matrisian, Lynn M.

PDF Url : ADA336736

Report Date : SEP 1997

Pagination or Media Count : 58

Abstract : We show that the metalloproteinase matrilysin dramatically accelerates the development of neu-induced mammary tumors by decreasing the time to tumor onset and increasing the percent of animals developing tumors. In addition, MMTV-matrilysin transgenic mice develop preneoplastic alveolar nodules in multiparous females. We speculated that the mechanism of tumor acceleration was via the induction of an EGF receptor signaling pathway, but an analysis of the interaction and phosphorylation of erbB family members demonstrated no evidence for activation of these pathways. Using human breast cancer cell lines, we demonstrated that the expression of matrilysin in MDA-MB-468 cells requires the presence of an EGF signaling pathway. However, in addition to the positive activation of matrilysin, the loss of a negative repressor of matrilysin expression is also required for constitutive matrilysin expression as demonstrated by fusion with the immortal breast epithelial cell line HBL 100. Determining: (1) the mechanism of matrilysin acceleration of mammary tumorigenesis and (2) characterization of the matrilysin repressor will be pursued in future studies.

Descriptors :   *NEOPLASMS, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, ACTIVATION, EPITHELIUM, ACCELERATION, FAMILY MEMBERS, CLINICAL MEDICINE, SIGNALS, ANIMALS, INFECTIOUS DISEASES, MEDICAL SERVICES, CELLS(BIOLOGY), SENSE ORGANS, RECEPTOR SITES(PHYSIOLOGY), PHOSPHORYLATION.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Stress Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE