title: Strong expression association between matriptase and its substrate prostasin in breast cancer.
abstract: Breast cancer tumorigenesis is accompanied by increased levels of extracellular proteases that are capable of remodeling the extracellular matrix as well as cleaving and activating growth factors and signaling receptors that are critically involved in neoplastic progression. Multiple studies implicate the membrane anchored serine protease matriptase (also known as MT-SP1 and epithin) in breast cancer. The pro-form of the GPI-anchored serine protease prostasin has recently been identified as a physiological substrate of matriptase and the two proteases are co-expressed in multiple healthy tissues. In this study, the inter-relationship between the two membrane-anchored serine proteases in breast cancer was investigated using breast cancer cell lines and breast cancer patient samples to delineate the association between matriptase and prostasin. We used Western blotting to determine the expression of matriptase and prostasin proteins in a panel of breast cancer cell lines and immunohistochemistry to assess the expression in serial sections from breast cancer tissue arrays. We demonstrate that the expression of matriptase and prostasin is closely correlated in breast cancer cell lines as well as in breast cancer tissue samples. Furthermore, matriptase and prostasin display a near identical spatial expression pattern in the epithelial compartment of breast cancer tissue. These data suggest that the matriptase-prostasin cascade might play a critical role in breast cancer.
authors.affiliation: Department of Pharmacology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bergum
authors.forename: Gina
authors.initials: G
authors.lastname: Zoratti
authors.forename: Julie
authors.initials: J
authors.lastname: Boerner
authors.forename: Karin
authors.initials: K
authors.lastname: List
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014018:Tissue Distribution; D000099271:Prostasin
chemical_list: D034741:RNA, Small Interfering; D012697:Serine Endopeptidases; D000099271:Prostasin; C485596:ST14 protein, human