title: ADAM-17 predicts adverse outcome in patients with breast cancer.
abstract: ADAM-17 is a matrix metalloproteinase-like enzyme involved in the release of several ligands that have been shown to promote both cancer formation and progression. These ligands include transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, epiregulin and tumor necrosis factor-alpha. In this investigation, we measured the expression of total ADAM-17 by enzyme-linked immunosorbent assay in 153 invasive breast cancers. We also measured the precursor and active forms by western blotting in 140 invasive breast cancers. Expression of ADAM-17 was significantly increased in high-grade compared with low-grade tumors and was independent of tumor size, lymph node metastasis and estrogen receptor status. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for breast cancer. Our results are further evidence that ADAM-17 is involved in breast cancer progression and thus provides further impetus for exploiting ADAM-17 as new target for cancer treatment.
authors.affiliation: Department of Pathology, Laboratory Medicine, Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: P M
authors.initials: PM
authors.lastname: McGowan
authors.forename: E
authors.initials: E
authors.lastname: McKiernan
authors.forename: F
authors.initials: F
authors.lastname: Bolster
authors.forename: B M
authors.initials: BM
authors.lastname: Ryan
authors.forename: A D K
authors.initials: AD
authors.lastname: Hill
authors.forename: E W
authors.initials: EW
authors.lastname: McDermott
authors.forename: D
authors.initials: D
authors.lastname: Evoy
authors.forename: N
authors.initials: N
authors.lastname: O'Higgins
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: M J
authors.initials: MJ
authors.lastname: Duffy
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000072198:ADAM17 Protein; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis
chemical_list: D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human