A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene.
Tumor cell invasion requires expression of degradative enzymes such as plasminogen activator, collagenase, and cathepsins. Cathepsin D, a lysosomal aspartic protease produced constitutively in human breast cancer cell lines, also has mitogenic activity in breast cancer cells. Additionally, high cathepsin D expression is associated with increased risk of metastasis in patients with node-negative breast cancer. Recently, a novel aspartic protease gene, ALP56 (aspartic-like protease 56kDa), has been identified. To examine possible interrelationships we quantitated ALP56 mRNA and cathepsin D mRNA in breast cancers using reverse transcription polymerase chain reaction. ALP56 mRNA expression was greater in cancers than in noncancerous tissues (p < 0.0001), as was expression of cathepsin D mRNA. ALP56 gene expression was dose-dependently down-regulated in T-47D breast cancer cells treated with estradiol, while cathepsin D was up-regulated. Expression of ALP56 mRNA in estrogen receptor (ER)-positive breast cancers was less than that in ER-negative cancers, and mRNA expression for ALP56 and cathepsin D did not correlate with one another. Thus ALP56 as well as cathepsin D may be a useful target molecule in breast cancer treatment.
Kondoh
Kei
K
Division of Laboratory Diagnosis, Department of Clinical Laboratory Medicine, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Tsuji
Naoki
N
Kamagata
Chinatsu
C
Sasaki
Masateru
M
Kobayashi
Daisuke
D
Yagihashi
Atsuhito
A
Watanabe
Naoki
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002402:Cathepsin D / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics*
D012333:RNA, Messenger; C411442:ALP56 enzyme; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D