Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells.
Array-based comparative genomic hybridization (array-CGH) has powerful potential for high-throughput identification of genetic aberrations in cell genomes. We identified high-level amplification of kallikrein (KLK) genes, which are mapped to 19q13.3 and belong to the serine protease family, in the course of a program to screen a panel of urinary bladder carcinoma cell lines for genomic copy number aberrations using our in-house CGH-array. Expression levels of KLK5, -6, -8 and -9 were significantly increased in three cell lines with copy number gains of these KLK genes. Knockdown of these KLK transcripts by specific small interfering RNA significantly inhibited the invasion of a bladder carcinoma cell line through Matrigel in vitro. Reverse transcription-polymerase chain reaction analysis of 42 primary bladder tumor samples showed that increased expression of KLK5 was frequently observed in invasive tumors (pT2-pT4) (14.3%, 6/42) compared with superficial tumors (pTa, pT1) (0%, 0/42; P = 0.0052), and expression levels of KLK5, -6, -8 and -9 mRNA were higher in invasive tumors than in superficial tumors (P < 0.0001, P = 0.0043, P = 0.0790 and P = 0.0037, respectively). These observations indicate that KLK5, -6, -8 and -9 may be the most likely targets of the 19q13.3 amplification, and may play a crucial role in promoting cancer-cell invasion in bladder tumor.
Shinoda
Yasuo
Y
Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Kozaki
Ken-Ichi
K
Imoto
Issei
I
Obara
Wataru
W
Tsuda
Hitoshi
H
Mizutani
Yoichi
Y
Shuin
Taro
T
Fujioka
Tomoaki
T
Miki
Tsuneharu
T
Inazawa
Johji
J
D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D005784:Gene Amplification; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009693:Nucleic Acid Hybridization; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
C400147:KLK5 protein, human; C103551:KLK6 protein, human; C094799:KLK8 protein, human; C410801:KLK9 protein, human; D007610:Kallikreins