Oct-4在激素非依赖性前列腺癌干细胞中的表达及意义

背景：干细胞特异性基因Oct-4在维持干细胞功能和调节干细胞的分化过程中起着关键性作用，了解前列腺癌干细胞中Oct-4的表达，对前列腺癌的预后、复发和耐药的评估具有重要意义。 目的：观察Oct-4在激素非依赖性前列腺癌干细胞中的表达。 设计、时间及地点：观察性实验，于2008-02/10在南昌大学第一附属医院中心实验室完成。 材料：取12例前列腺癌患者手术后组织标本，其中6例在手术前没有经过化疗和激素治疗，另外6例患者经过激素治疗出现抵抗而手术。 方法：制备前列腺癌组织单细胞悬液，流式细胞仪分选未经治疗前列腺癌和治疗后出现耐药的前列腺癌干细胞，RT-PCR和Western blot检测激素非依赖性前列腺癌Oct-4基因和蛋白的表达。 主要观察指标：激素依赖和非依赖性前列腺癌CD133+/CD44+以及CD133-/CD44-细胞的比例；Oct-4基因和蛋白在激素非依赖性前列腺癌CD133+/CD44+、CD133+/CD44-、CD133-/CD44+、CD133-/CD44-细胞的表达。 结果：流式细胞仪检测显示未经过治疗的前列腺癌CD133+/CD44+细胞占(0.83±0.21)%，而CD133-/CD44-细胞多达(95.62±1.35)%；治疗出现激素抵抗的前列腺癌CD133+/CD44+细胞为(54.62±0.86)%，而CD133-/CD44-细胞为(9.56±0.47)%；与其他亚群细胞相比，激素非依赖性前列腺癌CD133-/CD44-细胞Oct-4基因和蛋白显著降低(P < 0.01)；CD133+/CD44+细胞Oct-4基因和蛋白表达显著升高(P < 0.01)；而CD133+/CD44-和CD133-/CD44+细胞之间Oct-4基因和蛋白表达无显著差异(P > 0.05)。 结论：Oct-4在激素非依赖性前列腺癌干细胞中高表达，可能与前列腺癌的预后和耐药有关。

Oct-4 expression and significance in hormone independent prostatic cancer stem cells

BACKGROUND: Stem cell specific gene Oct-4 plays a key role in maintaining the function of stem cells and regulating the differentiation of stem cells. Therefore, understanding the expression of Oct-4 is important in prognosis, relapse and drug resistance evaluation of prostatic cancer. OBJECTIVE: To investigate the expression of Oct-4 in hormone independent prostatic cancer stem cells. DESIGN, TIME AND SETTING: Observation. The experiment was performed at the Central Laboratory of First Hospital of Nangchang University from February to October 2008. MATERIALS: A total of 12 tissue samples of prostatic cancer after operation were obtained, including 6 samples without chemotherapy nor hormone therapy before operation, and others that were operated after resisting to hormone therapy. METHODS: Single cell suspension of prostatic cancer was prepared. Untreated stem cells and those resisting to hormone therapy were selected according to the marker of cells surface with flow cytometry; the Oct-4 gene and protein expression in hormone independent prostatic cancer was examined by RT-PCR and Western blot. MAIN OUTCOME MEASURES: The proportion of CD133+/CD44+ and CD133-/CD44- cells in hormone dependent and independent prostatic cancer; the expression of Oct-4 gene and protein in CD133+/CD44+, CD133+/CD44-, CD133-/CD44+ and CD133-/CD44- of hormone independent prostatic cancer. RESULTS: Flow cytometry indicated that CD133+/CD44+ cells of non-treatment prostatic cancer account for (0.83±0.21)%, and CD133-/CD44- cells account for (95.62±1.35)%; CD133+/CD44+ cells of hormone resistance prostatic cancer after therapy accounted for (54.62±0.86)%, and CD133-/CD44- cells accounted for (9.56 ±0.47)%. Compared with other cell subsets, the expression of Oct-4 gene and protein in CD133-/CD44- cells of hormone independent prostatic cancer was significantly decreased (P < 0.01); while the expression of Oct-4 gene and protein in CD133+/CD44+ cells was significantly increased (P < 0.01); there was no significant difference between CD133+/CD44- and CD133-/CD44+ cells in the expression of Oct-4 gene and protein (P > 0.05). CONCLUSION: Oct-4 is highly expressed in hormone independent prostatic cancer stem cells, and possibly correlates with relapse and drug resistance of prostatic cancer.