Accession Number : ADA321395

Title :   A Novel 80kDa Matrix-Degrading Proteinase in Breast Cancer Invasion and Metastasis.

Descriptive Note : Annual rept. 1 Sep 95-30 Aug 96,

Corporate Author : LONG ISLAND JEWISH HOSPITAL NEW HYDE PARK NY

Personal Author(s) : Shi, Yuenian E.

PDF Url : ADA321395

Report Date : SEP 1996

Pagination or Media Count : 69

Abstract : Recently, we cloned and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we transfected a full-length TIMP-4 cDNA into MDA-MB-435 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected vs control clones in the mammary fat of athymic nude mice. Overexpression of TIMP-4 significantly inhibited tumor growth rates; reached (3.5-14)-fold smaller primary tumor volumes and at sacrifice; and gave lower rates of axillary lymph node and lung metastasis as compared with control clones. A high-throughput direct differential cDNA sequencing approach was employed to identify genes differentially expressed in normal breast as compared with breast cancer. Of many putative differentially expressed genes, a breast cancer specific gene BCSG1, which was expressed in high abundance in a breast cancer cDNA library but scarcely in a normal breast cDNA library, was identified as a putative breast cancer marker. In situ hybridization analysis demonstrated a stage-specific BCSGl expression: undetectable in normal or benign breast lesions, partial expression in ductal carcinoma in situ, but extremely high level in advanced infiltrating breast cancer. BCSG1 overexpression may indicate breast cancer malignant progression.

Descriptors :   *PEPTIDE HYDROLASES, *METASTASIS, *BREAST CANCER, TISSUES(BIOLOGY), HUMANS, ENZYMES, NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, LUNG, GENES, CLONES, MICE, INHIBITORS, IN VIVO ANALYSIS, LESIONS, MAMMARY GLANDS, GROWTH(PHYSIOLOGY), HYBRIDIZATION, FAT CELLS, LYMPH NODES, COLLAGENASE.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE