title: Expression and localization of endothelin-converting enzyme-1 in human prostate cancer.
abstract: Endothelin (ET)-1 can influence cancer invasion and metastasis by exerting an autocrine (epithelial) or paracrine (stromal) influence on growth. ET-1 is generated from big ET-1 by endothelin-converting enzyme (ECE)-1, which has four recognized isoforms, ECE-1a, ECE-1b, ECE-1c, and ECE-1d, differing only in their amino-terminal regions. This study investigated the expression and localization of the ECE-1 isoforms in prostate cancer (PC). The epithelial cell lines used were androgen-sensitive LNCaP, androgen-independent PC-3 and Du145, and nonmalignant transformed PNT1-a, PNT2-C2, and P4E6 prostate cells. Primary cells derived from malignant and benign tissue from radical prostatectomies were also exploited. Previously, we reported increased ECE-1 expression in androgen-independent PC cell lines, as compared with androgen-sensitive cells. Our present data show that transcripts for all ECE-1 isoforms were present in all epithelial cell lines analyzed. However, only the ECE-1c protein was detectable in PC-3, Du145, PNT2-C2, and PNT1-a cells. ECE-1c localized to both the cell surface and intracellular compartments in individual cell lines. In primary stromal cells, all individual ECE-1 isoforms were expressed at the mRNA level, with the exception of ECE-1a. ECE-1b and ECE-1c protein levels were higher in malignant stromal cells, as compared with benign cells. In stroma, ECE-1c protein was localized to the cell surface, with filamentous immunoreactivity throughout the cell, whereas ECE-1b immunoreactivity was punctate throughout the cytoplasm. The upregulation of the ECE-1c isoform in PC cell lines is being investigated further.
authors.affiliation: Proteolysis Research Group, School of Biochemistry & Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom. bmblad@bmb.leeds.ac.uk
authors.forename: Louise A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Maitland
authors.forename: Paul
authors.initials: P
authors.lastname: Berry
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Turner
authors.forename: Badar A
authors.initials: BA
authors.lastname: Usmani
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D000072396:Endothelin-Converting Enzymes; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes