title: Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines.
abstract: Four different human breast cancer cell lines were examined to search for genes associated with tumor growth and metastasis. Each of these cell lines, MDA-MB-453, MCF-7, MDA-MB-231 and MDA-MB-435, displays different phenotypic characteristics ranging from poorly to highly tumorigenic and metastatic. The differences in gene expression profiles of these cell lines generated by differential display technique should allow one to identify candidates as putative oncogenes or tumor/metastasis suppressor genes. A novel cDNA expressed in the highly tumorigenic and metastatic cell line, MDA-MB-435, was identified and isolated by this approach. The function for this gene, designated ALP56 (aspartic-like protease 56 kDa), in tumor progression is suggested by the homology of the encoded protein to aspartic proteases, such as cathepsin D. The amino acid residues in two catalytic domains of this family are highly conserved in those domains of ALP56. Northern hybridization indicated that the expression of ALP56 is associated with growth and metastasis of MDA-MB-435 tumors in immunodeficient mice. In situ hybridization of biopsies from breast cancer and colon cancer patients indicated that ALP56 is upregulated in human primary tumors and liver metastasis. These results suggest that this novel gene correlates with human tumor progression.
authors.affiliation: Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
authors.forename: H
authors.initials: H
authors.lastname: Xin
authors.forename: J C
authors.initials: JC
authors.lastname: Stephans
authors.forename: X
authors.initials: X
authors.lastname: Duan
authors.forename: G
authors.initials: G
authors.lastname: Harrowe
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: U
authors.initials: U
authors.lastname: Grieshammer
authors.forename: C
authors.initials: C
authors.lastname: Kingsley
authors.forename: K
authors.initials: K
authors.lastname: Giese
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D019556:COS Cells; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; C411442:ALP56 enzyme; D016282:Aspartic Acid Endopeptidases