BACKGROUND: The process of proteolysis is important at several stages of the metastatic cascade. A balance between the expression of the genes encoding endogenous proteinases and inhibitors exists and when the production of proteinases exceeds that of inhibitors proteolysis occurs. AIMS: To determine whether differences in the profile and activity of proteinases and inhibitors exist within breast tumour tissue (n = 51), surrounding background breast tissue (n = 43), normal breast tissue from breast reduction mammoplasty operations (n = 10), and cells of the breast cancer cell line, MCF-7. METHODS: Proteinase (matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, urokinase-type plasminogen activator (uPA), and tissue-type PA (tPA)) and inhibitor (tissue inhibitor of metalloproteinases; TIMP-1 and TIMP-2) expression and proteinase activity were compared using substrate zymography, western blotting, immunohistochemistry, and quenched fluorescent substrate hydrolysis. RESULTS: The presence of all proteinases and inhibitors was greater in breast tumour tissue when compared with all other types of breast tissue (p < 0.05). The activity of total MMPs as determined by quenched fluorescent substrate hydrolysis was also greater in breast tumours (p < 0.05). CONCLUSIONS: There is increased proteolysis in human breast tumours when compared with other breast tissues.
BACKGROUND: The process of proteolysis is important at several stages of the metastatic cascade. A balance between the expression of the genes encoding endogenous proteinases and inhibitors exists and when the production of proteinases exceeds that of inhibitors proteolysis occurs. AIMS: To determine whether differences in the profile and activity of proteinases and inhibitors exist within breast tumour tissue (n = 51), surrounding background breast tissue (n = 43), normal breast tissue from breast reduction mammoplasty operations (n = 10), and cells of the breast cancer cell line, MCF-7. METHODS:Proteinase (matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, urokinase-type plasminogen activator (uPA), and tissue-type PA (tPA)) and inhibitor (tissue inhibitor of metalloproteinases; TIMP-1 and TIMP-2) expression and proteinase activity were compared using substrate zymography, western blotting, immunohistochemistry, and quenched fluorescent substrate hydrolysis. RESULTS: The presence of all proteinases and inhibitors was greater in breast tumour tissue when compared with all other types of breast tissue (p < 0.05). The activity of total MMPs as determined by quenched fluorescent substrate hydrolysis was also greater in breast tumours (p < 0.05). CONCLUSIONS: There is increased proteolysis in humanbreast tumours when compared with other breast tissues.
Authors: Karl E Miletti-González; Kyle Murphy; Muthu N Kumaran; Abhilash K Ravindranath; Roman P Wernyj; Swayamjot Kaur; Gregory D Miles; Elaine Lim; Rigel Chan; Marina Chekmareva; Debra S Heller; David Foran; Wenjin Chen; Michael Reiss; Elisa V Bandera; Kathleen Scotto; Lorna Rodríguez-Rodríguez Journal: J Biol Chem Date: 2012-03-20 Impact factor: 5.157
Authors: Cory M Yamashita; Lior Dolgonos; Rachel L Zemans; Scott K Young; Jennifer Robertson; Natalie Briones; Tomoko Suzuki; Megan N Campbell; Jack Gauldie; Derek C Radisky; David W H Riches; Guoying Yu; Naftali Kaminski; Christopher A G McCulloch; Gregory P Downey Journal: Am J Pathol Date: 2011-08-24 Impact factor: 4.307
Authors: Laetitia Devy; Shafaat A Rabbani; Mark Stochl; Mary Ruskowski; Ian Mackie; Laurent Naa; Mark Toews; Reinoud van Gool; Jie Chen; Art Ley; Robert C Ladner; Daniel T Dransfield; Paula Henderikx Journal: Neoplasia Date: 2007-11 Impact factor: 5.715