Accession Number : ADA334431

Title :   Regulation of Membrane Proteases Associated with Breast Cancer.

Descriptive Note : Final rept. 1 Aug 94-31 Jul 97

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Goldstein, Leslie

PDF Url : ADA334431

Report Date : AUG 1997

Pagination or Media Count : 23

Abstract : Seprase is a homodimeric 170 kDa integral membrane gelatinase whose expression correlates with the invasiveness of the human melanoma cell line LOX. We are interested in determining its potential role in breast cancer metastasis since seprase mRNA has been detected in the breast carcinoma cell lines MDA-MB-436 and Hs 578T. Sequence analysis of a cDNA clone from LOX indicates that it is a type I integral membrane glycoprotein that belongs to the family of nonclassical serine hydrolases. Additional sequence analysis of seprase cDNA clones from LOX, MDA-MB-436 and the fibroblast line WI-38 strongly suggests that seprase and fibroblast activation protein a are the same protein. We have produce stable seprase transfectants for the breast carcinoma cell lines MCF-7,MDA-MB-23 1 and MDA-MB-43 which will be tested in in vitro matrix degradation/invasion assay systems. Unexpectedly, we have discovered that seprase pre-mRNA undergoes alternative exon splicing giving rise to a truncated mRN which cannot encode the membrane form of seprase but potentially encodes a truncated intracellular form of seprase. Preliminary RNA analysis of Hs 578Bst and Hs 578T suggests that the truncated RNA is up regulated in the breast carcinoma.

Descriptors :   *MEMBRANES(BIOLOGY), *RIBONUCLEIC ACIDS, *MAMMARY GLANDS, *PEPTIDE HYDROLASES, *SERINE, *BREAST CANCER, ACTIVATION, ENZYMES, PROTEINS, NEOPLASMS, SEQUENCES, CLONES, FIBROBLASTS, TRUNCATION, GELATINS, LIQUID OXYGEN, HYDROLASES, METASTASIS.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE