激素难治性前列腺癌组织中雄激素受体蛋白表达的研究

背景与目的:近来有研究报道,在激素难治性前列腺癌(hormonerefractoryprostatecarcinoma,HRPC)中发现有雄激素受体(androgenreceptor,AR)基因扩增,并提出AR基因扩增可能是导致激素治疗失败的一个新的分子机制。本研究拟对前列腺癌在激素治疗前和治疗失败后的AR蛋白表达作定量测定,进一步探讨AR表达与HRPC发生的关系。方法:采用放射配体结合分析方法测定28例晚期前列腺癌患者在激素治疗前以及治疗失败后原发癌组织中的AR蛋白含量。结果:28例前列腺癌在治疗前、后癌组织中的AR蛋白平均水平分别为(390.0±204.1)和(690.4±444.0)fmol/mgProtein,两者间差异有显著性(P<0.001)。其中10例在治疗后12个月内复发,其AR蛋白平均水平在治疗前、后分别为(398.2±199.5)和(448.2±274.1)fmol/mgProtein两者间差异无显著性(P>0.20),其余18例的AR蛋白平均水平在治疗前、后分别为(386.4±212.3)和(824.9±468.6)fmol/mgProtein,两者间差异有显著性(P<0.001)。结论:AR蛋白水平升高可能是前列腺癌对激素治疗不敏感的原因之一。

Expression of androgen receptor protein in hormone refractory prostate cancer

BACKGROUND & OBJECTIVE: It was reported that androgen receptor (AR) gene amplification was found in hormone refractory prostate (HRPC) and it has been thought to be a possible molecular mechanism for the treatment failure. In this article, the expression of AR protein before and after hormone therapy was examined quantitatively in order to further clarify the relationship between AR expression and the genesis of HRPC. METHODS: AR protein content was determined using radioligand binding assay before and after hormone therapy in 28 patients with advanced prostate cancer. RESULTS: The average levels of AR protein before and after hormone therapy were 390.0 +/- 204.1 fmol/mg protein and 690.4 +/- 444.0 fmol/mg protein, respectively (P < 0.001). In 10 patients whose diseases recurred in 12 months after therapy, the mean levels of AR protein before and after therapy were 398.2 +/- 199.5 fmol/mg protein and 448.2 +/- 274.1 fmol/mg protein, respectively (P > 0.20). In other 18 patients with response duration more than 12 months, the mean levels of AR protein before and after therapy were 386.4 +/- 212.3 fmol/mg protein and 824.9 +/- 468.6 fmol/mg protein, respectively (P < 0.001). CONCLUSION: The elevation of AR protein level was most likely to occur in the prostatic tumors that had good response to hormone therapy and might be involved in the genesis of HRPC.