A lysosomal pepstatin-insensitive proteinase as a novel biomarker for breast carcinoma.
Lysosomal proteinases play an important role in the turnover of intracellular proteins, and acidic proteinases such as cathepsin D are known to be increased in breast carcinoma. In the present study the activity of a newly discovered acidic lysosomal pepstatin-insensitive proteinase (CLN2p) was measured in breast tissues by the most sensitive and highly specific assay that we had developed for the diagnosis of late-infantile neuronal ceroid lipofuscinosis (LINCL) (2). Samples from eight normal subjects undergoing reductive mammoplasty and 200 patients with primary breast carcinoma were analyzed. The results suggest a two- to seventeen-fold higher CLN2p activity in tumors, which was significantly and positively correlated with already known breast cancer biomarkers such as levels of cathepsin D, estrogen receptor and progesterone receptor. These results suggest a diagnostic and prognostic potential for this novel acid proteinase in breast cancer.
Junaid
M A
MA
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, USA.
Clark
G M
GM
Pullarkat
R K
RK
D000626:Aminopeptidases; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004273:DNA, Neoplasm / Q000032:analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D010436:Pepstatins / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000032:analysis* / Q000302:isolation & purification; D011003:Ploidies; D011480:Protease Inhibitors / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016196:S Phase; D012680:Sensitivity and Specificity; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010436:Pepstatins; D011480:Protease Inhibitors; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000091346:Tripeptidyl-Peptidase 1; C014195:Streptomyces pepsin inhibitor; D066246:ErbB Receptors; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D002402:Cathepsin D; C031375:pepstatin