ADAM-17 expression in breast cancer correlates with variables of tumor progression.
The ADAMs are a family of membrane proteins possessing a disintegrin and metalloprotease domain. One of their main functions is shedding of membrane proteins. The aim of this study was to test the hypothesis that ADAM-17 (also known as tumor necrosis factor-alpha converting enzyme) is involved in breast cancer progression. Overexpression of ADAM-17 in MCF-7 breast cancer cells increased in vitro invasion and proliferation, whereas down-regulation of ADAM-17 expression in MDA-MB-435 cells decreased invasion and proliferation. At both mRNA and protein levels, ADAM-17 expression was significantly up-regulated in breast cancer compared with normal breast tissue. Using Western blotting, ADAM-17 protein in breast cancer was shown to exist in two forms migrating with approximate molecular masses of 100 and 120 kDa. Based on their known molecular mass, these bands were taken to represent the active and precursor forms of ADAM-17, respectively. The proportion of active to total ADAM-17 increased progressively from normal breast tissue to primary breast cancer to lymph node metastases (P = 0.017, Kruskal-Wallis test). In primary cancers, the active form was expressed more frequently in node-positive compared with node-negative tumors (P = 0.034, chi(2) test). Furthermore, in primary carcinomas, both forms of ADAM-17 correlated significantly (Spearman correlation analysis) with levels of urokinase plasminogen activator (precursor form: r = 0.246, P = 0.032, n = 83 and active form: r = 0.428, P = 0.0001, n = 83) and proliferating cell nuclear antigen (precursor form: r = 0.524, P < 0.0001, n = 73 and active form: r = 0.365, P = 0.002, n = 73). Our results support the hypothesis that ADAM-17 is involved in breast cancer progression.
McGowan
Patricia M
PM
Department of Pathology and Laboratory Medicine, St. Vincent's University Hospital, Ireland.
Ryan
Bríd M
BM
Hill
Arnold D K
AD
McDermott
Enda
E
O'Higgins
Niall
N
Duffy
Michael J
MJ
D051722:ADAM Proteins / Q000235:genetics*; D000072198:ADAM17 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D012333:RNA, Messenger; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human