Study of gentic and epigenetic alterations in prostatic cancer using DNA microarray method.

日本的前列腺癌发病率和由此导致的死亡率低于西方国家。为了阐明这背后的原因，我们调查了日本患者前列腺癌的遗传特征。应用比较基因组杂交技术对27例日本前列腺癌患者进行了检测。13q缺失的频率可能意味着日本和西方国家前列腺癌生物学行为的差异。为了阐明一种阵列比较基因组杂交(CGH)技术，我们对11例前列腺癌进行了283个特异基因的阵列比较基因组杂交(CGH)，并与比较基因组杂交(常规CGH)和利用小卫星DNA标记进行杂合性缺失(LOH)分析进行了比较。当两种CGH技术的结果与杂合性缺失分析的结果相比较时，阵列CGH的符合率显著高于常规CGH(93.4%vs.72.2%，p&lt；0.05)。我们检测了表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼(Iressa，ZD1839)对三种人前列腺癌LNCaP(激素依赖型生长)、PC-3(激素非依赖性生长)和DU-145细胞的抑制作用及其机制。Gefinitib处理组对各细胞系均有明显的生长抑制作用，且呈剂量依赖关系。基因芯片实验显示，有几个基因表达下调。

Incidence of prostate cancer in Japan and resultant mortality rates are lower than in Western countries. To elucidate the reasons behind this, the genetic characteristics of prostate cancer in Japanese patients were investigated. Comparative genomic hybridization was applied in 27 cases of prostate cancers in Japanese patients. The frequency of 13q loss may imply differences in biological behavior of prostate cancer between Japan and Western coutries. To clarify a array comparative genomic hybridization(CGH) technique, we applied array CGH spotted with 283 specific genes to 11 clinical prostate cancers, and the results were compared with comparative genomic hybridization (conventional CGH) and loss of heterozygosity (LOH) analysis using miciosatellite DNA markers. When the results of both CGH techniques were compared with those of LOH analysis, the correspondence rate of array CGH was significantly higher than that of conventional CGH (93.4% vs. 72.2%, p<0.05).We examined the antiproliferative effects and mechanism of gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) on three human prostate cancer cell lines, LNCap (hormon-dependent growth), PC-3 (hormone-independent growth) and DU-145. A significant dose-dependent growth-inhibitory effect was observed in the gefinitib treatment group for each cell lines. cDNA microarray experiments showed that several genes were down regulated.