Alterations in cathepsin L expression in lung cancers.
We herein investigated the potential role of cathepsin L in lung carcinogenesis. Lung cancer cell lines and surgically resected tumors were examined for the expression of the cathepsin L protein and copy number alterations in its gene locus. Cathepsin L was stably expressed in bronchiolar epithelial cells. Neoplastic cells expressed cathepsin L at various levels, whereas its expression was completely lost in most of the lung cancer cell lines (63.6%, 7/11) examined. Furthermore, expression levels were lower in a large fraction of lung tumors (69.5%, 139/200) than in bronchiolar epithelia. The expression of cathepsin L was lost in some tumors (16.0%, 32/200). In adenocarcinomas, expression levels were significantly lower in high-grade tumors than in low-grade tumors (one-way ANOVA, P < 0.0500). Copy number alterations were found in 18.0% (36 [32 gain + 4 loss] /200) of lung tumors. No relationship existed between cathepsin L protein expression levels and the copy number of its gene locus (Spearman's rank-order correlation, P = 0.3096). Collectively, these results suggest that the down-regulated expression of cathepsin L, which is caused by an undefined mechanism other than copy number alterations, is involved in the progression of lung adenocarcinomas.
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Koji
K
Okudela
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Hideaki
H
Mitsui
Department of Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Tetsukan
T
Woo
Division of General Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan.
Hiromasa
H
Arai
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takehisa
T
Suzuki
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Mai
M
Matsumura
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|Department of Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Yoko
Y
Kojima
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Shigeaki
S
Umeda
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yoko
Y
Tateishi
Department of Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Munetaka
M
Masuda
Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Kenichi
K
Ohashi
D000230:Adenocarcinoma / Q000503:physiopathology*; D000077192:Adenocarcinoma of Lung; D056668:Cathepsin L / Q000235:genetics*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008175:Lung Neoplasms / Q000503:physiopathology*
D056668:Cathepsin L
carcinogenesis; cathepsin L; lung cancer