| Project/Area Number |
18591760
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kagoshima University |
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Principal Investigator |
HIDEKI Enokida Kagoshima University, Graduate School of Medical and Dental Sciences, Senior Assistant Professor (80347103)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Kenryu Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor (80264422)
NAKAGAWA Masayuki Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (90164144)
久保 博幸 鹿児島大学, 大学院医歯学総合研究科, 助手 (60336344)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | prostate cancer / biomarker / methvlation |
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| Research Abstract |
cDNA microarray analysis revealed that 18 genes were more than 1.5-fold in the prostate cancer (PC) cell line (LNCaP and PC3) after de-methylaing agent (5-aza-dC). Methylation frequencies of adenomatous polyposis coli (APC), multidrug resistance one (MDR1), gkutathione S-transferase pi (GSTP1) in prostate cancer were significantly correlated not only to advancing pathological features but also cigarette smoking status. Our data suggests that cigarette smoking contributes to pathogenesis in human PC through these genes methylation. Metallothioneins (MTs) are a family of low molecular weight, a cystine rich, and heavy metal binding proteins. We found unique expression pattern of metallothionein 1G (MT1G) in the PC cell line (LNCaP and PC3) after de-methylaing agent (5-aza-dC). Alterative MTG1 expression was not found in hormone sensitive PC cell (LNCaP), but it markedly increased in hormone resistant PC cell (PC3) after 5-aza-dC treatment. In clinical PC samples, the frequency of MT1G pr
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omoter hypermethylation was significantly higher in benign prostate hypertrophy (BPH) than in PC samples (44/69 (63.8%) vs. 37/177 (20.9%), respectively). Bisulfite DNA sequencing comfirmed that there were C-peak at every CpG sites in the mathylated samples. Interestingly, the metylation frequency in advanced PC samples was significantly higher than in localized PCs. Immunohistochemistry demonstrated that the number of ssDNA positive cells were significantly higher in unmethylated samples in methylated samples (5.99 ±1.35, 4.08 ± 3.58, respectively, p=0.011). There was no difference in the number of PCNA positive cells between the groups. Our data suggests a more complex role of MT1G methylation underlying PC progression. Further more, we extracted DNA from urine sediment after prostate massage. Followed by the bisulfite-treated samples were subjected to quantitative methylation specific PCR. GSTP1 hypermethylation was detected in 13 of 60 urine samples (sensitivity of 21.7%), whereas only one of 30 BPH samples was positively detected (specificity of 96.7%). Further study is needed to improve detection sensitivity. Less
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