Open Access

CpG hypermethylation of collagen type I α 2 contributes to proliferation and migration activity of human bladder cancer

  • Authors:
    • Katsuhisa Mori
    • Hideki Enokida
    • Ichiro Kagara
    • Kazumori Kawakami
    • Takeshi Chiyomaru
    • Shuichi Tatarano
    • Kazuya Kawahara
    • Kenryu Nishiyama
    • Naohiko Seki
    • Masayuki Nakagawa
  • View Affiliations

  • Published online on: Monday, June 1, 2009
  • Pages: 1593-1602 DOI: 10.3892/ijo_00000289

Abstract

In our microarray screening of methylated genes in bladder cancer (BC), the collagen type 1 α 2 (COL1A2) gene was the most up-regulated among the 30,144 genes screened. We hypothesize that inactivation of the COL1A2 gene through CpG methylation contributes to proliferation and migration activity of human BC. We subjected a bladder cancer cell line (BOY) and 67 BC specimens and 10 normal bladder epitheliums (NBEs) to conventional or real-time methylation quantitative polymerase chain reaction (PCR) and to real-time reverse transcriptase (RT)-PCR. We also established a stable COL1A2 transfectant for evaluating cell proliferation and migration activity. After 5-aza-dC treatment, the expression levels of COL1A2 mRNA transcript markedly increased in BOY. Our cell proliferation assays consistently demonstrated growth inhibition in the COL1A2 transfectant compared with control and wild-type BOY cells (p<0.0001). Wound healing assays also showed significant wound healing inhibition in the COL1A2 transfectant compared to the counterparts (p=0.0016). We demonstrated by bisulfite DNA sequencing that the promoter hypermethylation of COL1A2 was a frequent event in clinical BCs. The methylation index of COL1A2 was significantly higher in the 67 BCs than in the 10 NBEs (p=0.0011). Conversely, COL1A2 mRNA transcript was significantly lower in the BCs than in the NBEs (p=0.0052). The mechanism of COL1A2 down-regulation in BC is through CpG hypermethylation of the promoter region. COL1A2 gene inactivation through CpG hypermethylation may contribute to proliferation and migration activity of BC.

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June 2009
Volume 34 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
Ranked #30/211 Oncology
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APA
Mori, K., Enokida, H., Kagara, I., Kawakami, K., Chiyomaru, T., Tatarano, S. ... Nakagawa, M. (2009). CpG hypermethylation of collagen type I α 2 contributes to proliferation and migration activity of human bladder cancer. International Journal of Oncology, 34, 1593-1602. http://dx.doi.org/10.3892/ijo_00000289
MLA
Mori, K., Enokida, H., Kagara, I., Kawakami, K., Chiyomaru, T., Tatarano, S., Kawahara, K., Nishiyama, K., Seki, N., Nakagawa, M."CpG hypermethylation of collagen type I α 2 contributes to proliferation and migration activity of human bladder cancer". International Journal of Oncology 34.6 (2009): 1593-1602.
Chicago
Mori, K., Enokida, H., Kagara, I., Kawakami, K., Chiyomaru, T., Tatarano, S., Kawahara, K., Nishiyama, K., Seki, N., Nakagawa, M."CpG hypermethylation of collagen type I α 2 contributes to proliferation and migration activity of human bladder cancer". International Journal of Oncology 34, no. 6 (2009): 1593-1602. http://dx.doi.org/10.3892/ijo_00000289