Detection of gene marker for hormone-resistance of prostatic carcinoma

本实验室建立的雄激素非依赖性前列腺癌细胞系（LNCaP-N）的DNA芯片结果显示，与雄激素依赖性亲本细胞系（LNCaP）相比，LNCaP-N强表达胰岛素样生长因子结合蛋白2（IGFBP-2）。因此，我们采用真实的时间定量RT-PCR方法，对39例BPH和69例未治疗的前列腺癌患者的前列腺穿刺活检标本中IGFBP-2的表达进行了研究。在21例接受激素治疗的前列腺癌病例中，从经尿道切除术中获得存档样本。BPH组IGFBP-2表达水平明显高于未治疗的前列腺癌组（P<0.0001）。在前列腺癌中，IGFBP-2表达水平在低级别病例和高级别病例之间没有差异。并且，我们没有显示局部病例和晚期病例的IGFBP-2表达水平之间的显著差异。IGFBP-2的表达水平与乳腺癌的生存率和复发率无关。另一方面，我们比较了4例转移性前列腺癌患者的回肠骨髓和原发灶IGFBP-2的表达水平，骨髓IGFBP-2的表达水平有低于原发灶的趋势。在21例接受激素治疗的乳腺癌中，IGFBP-2的表达水平高于未治疗的乳腺癌。此外，我们还研究了胸苷酸合成酶和二氢嘧啶脱氢酶mRNA在前列腺癌中的表达水平，但未发现它们与前列腺癌临床病理因素之间的相关性。

As a result of DNA microarrays for androgen-independent prostatic carcinoma cell line (LNCaP-N) established in our laboratory, LNCap-N strongly expressed insulin like growth factor-binding protein 2 (IGFBP-2) compared with androgen-dependent parent cell line (LNCaP). Therefore we investigated the expressions of IGFBP-2 in human prostate diseases by real time quantitative RT-PCR method.Archival samples were obtained from prostate needle biopsy specimens in 39 BPH cases and 69 nontreatment-prostatic carcinoma cases. In 21 prostate carcinoma cases treated hormone therapy, archival samples were obtained from transurethral resection. The IGFBP-2 expression levels in BPH cases was statistically higher than those in no-treated prostate carcinoma cases (P<0.0001). In prostate carcinomas, there was no difference between the IGFBP-2 expression levels of low-grade cases and those of high-grade cases. And, we did not show significant difference between the IGFBP-2 expression levels of localized cases and those of advanced cases. Moreover, the IGFBP-2 expression levels did not associated to the cause-specific survival rate and recurrence rate. On the other hand, we compared the IGFBP-2 expression levels with ileum bone marrow and with primary tumor lesion in 4 metastatic prostatic carcinoma cases, and that of bone marrow tended to be low than that of primary tumor. In 21 cases performed hormone therapy, the IGFBP-2 expression levels were higher than those of no-treated carcinoma cases. These results showed statistically significant difference (P=0.0158).Furthermore, we studyed mRNA expression level of thymidylate synthase and dihydropynmidine dehydrogenase for prostatic carcinoma, but did not recognize the correlation between clinicopathologic factor.