Search for molecular marker for predicting progression in prostate cancer by competitive PCR analysis

通过竞争性 PCR 分析寻找预测前列腺癌进展的分子标记

• 批准号: 08671841
• 负责人: EGAWA Shin
• 金额: $ 0.7万
• 依托单位: KITASATO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671841/
• 关键词: Prostate cancer; competitive PCR; molecular marker; racial difference; point mutation; 点突然変異定性; 生物学的活性; genomic instability; DNA ploidy; TGF-beta1

Prostate cancer is unique among potentially lethal human malignancies in terms of striking differences in the mortality rate and incidence according to country. Environmental factors and differences in the probability of occurrence in genetic events essential for tumor progression may possibly be factors responsible for cancer cell proliferation. However, molecular mechanisms for prostate carcinogenesis is very little understood despite these considerations. The PCR-based microsatellite instability assay was used to screen 66 patients with prostatic adenocarcinoma for possible mutator phenotype at 8 microsatellite marker loci on 5 chromosomes in our previous study. Unstable microsatellites was detected in 13 of the 66 (19.7%) patients. Somatic instability may be related to a phenotype with the ability to invade outside the confines of the prostate gland. We could not find any distinct differences in volume, distribution or DNA ploidy status of a tumor from western counterpart. Examination was made of structural abnormality of the androgen receptor (AR) gene in 29 human prostate cancer. A point mutation was found in the exon D hormone-binding domain of AR leading to substitution of glutamine (CAG) for wild-type arginine (CGG) at codon 629 in 1 (3.4%) hormone-independent stage D2 patient. Microsatellite instability was detected in 5 of the 27 (18.5%)patients, 1 of 6 (16.7%) hormon independent stage D2 and 4 of 2l (19.0%) hormdne-dependent and non-treated prostate cancer patients. Competitive PCR method was employed to further investigate the pattern of expression of kai-1, bcl2, TGFbeta and PTHrP in human prostate cancer. No specific pattern of expression was determined.

根据国家的说法，前列腺癌在潜在致命的人类恶性肿瘤中是独一无二的，因为死亡率和发病率存在显着差异。环境因素和肿瘤进展所必需的基因事件发生概率的差异可能是导致癌细胞增殖的因素。然而，尽管有这些考虑，前列腺癌发生的分子机制却知之甚少。应用聚合酶链式反应技术对66例前列腺癌患者进行了5条染色体上8个微卫星标记基因座突变表型的筛查。在66例患者中，有13例(19.7%)检测到不稳定微卫星。躯体不稳定可能与一种具有侵袭能力的表型有关，该表型具有侵袭前列腺外部的能力。我们没有发现肿瘤的体积、分布或DNA倍体状态与西方同行有任何明显的差异。对29例前列腺癌患者雄激素受体(AR)基因结构异常进行了检测。在1例(3.4%)激素非依赖性D2患者中，发现AR外显子D激素结合区发生点突变，导致629位密码子上的谷氨酰胺(CAG)取代野生型精氨酸(CGG)。27例前列腺癌患者中有5例(18.5%)检测到微卫星不稳定性，6例激素非依赖期前列腺癌患者中有1例(16.7%)存在微卫星不稳定性，21例激素依赖型前列腺癌患者中有4例(19.0%)存在微卫星不稳定性。应用竞争性聚合酶链式反应技术进一步研究KAI-1、BCL2、TGFβ和PTHrP在前列腺癌组织中的表达。目前还没有确定具体的表达模式。

项目成果

Uchida, T.,: "Mutation and microsatellite instability anaysis of the andorogen receptor gene in human prostate cancer." Int.J.Oncol.11. 551-556 (1997)

Uchida, T.：“人类前列腺癌雄激素受体基因的突变和微卫星不稳定性分析。”

Uchida Toyoaki: "Mutation and microsatellite instability analysis of the androgen receptor gene in human prostate cencer." Int.J.Oncolo.11. 551-556 (1997)

Uchida Toyoaki：“人类前列腺癌雄激素受体基因的突变和微卫星不稳定性分析。”

Shin Egawa: "Deoxyribonucleic acid ploidy status as no basis for pathologic stage prediction in clinically resectable prostate cancer." Urology. 47. 548-552 (1996)

Shin Ekawa：“脱氧核糖核酸倍性状态不能作为临床可切除前列腺癌病理分期预测的基础。”

Shin Egawa: "Significance of preoperative parameters for predicting tumor volume in nonpalpable prostate cancer." Jpn.J.Clin.Oncol.25. 356-361 (1996)

Shin Ekawa：“术前参数对于预测不可触及的前列腺癌肿瘤体积的意义。”

Egawa, S.,: "Free versus total serum prostate specific antigen ratio for differential diagnosis of prostate cancer in japan." Cancer. 79. 90-98 (1997)

Ekawa, S.：“日本游离前列腺特异性抗原与总血清前列腺特异性抗原的比率用于前列腺癌的鉴别诊断。”