Proteolysis in human breast cancer.
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.


OBJECTIVE
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.
Garbett
E A
EA
Professorial Unit of Surgery, North Tees General Hospital, Stockton on Tees, UK. drlizbaker@yahoo.co.uk
Reed
M W
MW
Stephenson
T J
TJ
Brown
N J
NJ
D000704:Analysis of Variance; D015153:Blotting, Western; D001940:Breast / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000032:analysis* / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000032:analysis*; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis
D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1