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，我们研究了日本前列腺癌患者的遗传特征。比较基因组杂交技术应用于27例日本前列腺癌患者。13q丢失的频率可能暗示了日本和西方国家前列腺癌生物学行为的差异。为了阐明阵列比较基因组杂交（CGH）技术，我们将283个特定基因的阵列比较基因组杂交（CGH）应用于11例临床前列腺癌，并将结果与比较基因组杂交（常规CGH）和杂合性缺失（LOH）分析进行比较。将两种CGH技术的结果与LOH分析结果进行比较，阵列CGH的对应率显著高于常规CGH （93.4% vs. 72.2%, p<0.05）。我们研究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LNCap（激素依赖型生长）、PC-3（激素依赖型生长）和DU-145三种人前列腺癌细胞系的抗增殖作用及其机制。吉非尼替治疗组对各细胞系均有明显的剂量依赖性生长抑制作用。cDNA微阵列实验显示，多个基因下调。

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.