Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells

Yasuo Shinoda, Ken Ichi Kozaki, Issei Imoto, Wataru Obara, Hitoshi Tsuda, Yoichi Mizutani, Taro Shuin, Tomoaki Fujioka, Tsuneharu Miki, Johji Inazawa

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33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1078-1086
Number of pages9
JournalCancer Science
Volume98
Issue number7
DOIs
Publication statusPublished - Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shinoda, Y., Kozaki, K. I., Imoto, I., Obara, W., Tsuda, H., Mizutani, Y., Shuin, T., Fujioka, T., Miki, T., & Inazawa, J. (2007). Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells. Cancer Science, 98(7), 1078-1086. https://doi.org/10.1111/j.1349-7006.2007.00495.x