Mohler James L, Morris Tammy L, Ford O Harris, Alvey Rudolf F, Sakamoto Choitsu, Gregory Christopher W
Department of Surgery, Division of Urology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Prostate. 2002 Jun 1;51(4):247-55. doi: 10.1002/pros.10086.
The human prostate cancer xenograft, CWR22, similar to most human prostate cancers, regresses after castration and recurs several months after the removal of androgen. Genes uniquely associated with proliferation were identified by comparison of tumors that exist in androgen absence but differ in proliferative capacity.
cDNA libraries from CWR22 tumors from 20-day castrate mice (proliferation undetectable) and recurrent CWR22 tumors (proliferation rate similar to androgen-dependent CWR22) were compared to evaluate the possibility that proliferation is triggered by either gain of function or loss of suppression. Differentially expressed genes were evaluated further for their temporal association with the onset of cellular proliferation using northern and western analysis and immunohistochemistry of a series of CWR22 tumors that spanned the transition from androgen-dependent to recurrent growth.
Subtractive hybridization identified 11 candidate genes from among 1,057 clones examined. Northern analysis confirmed differential expression of 8 genes. Western analysis revealed an association between tomoregulin, translation elongation factor-1 alpha (EF-1 alpha), Mxi-1, and thioredoxin-binding protein 2/vitamin D up-regulated protein, and the onset of recurrent growth. Immunohistochemistry revealed expression of tomoregulin, EF-1 alpha, Mxi-1, and thioredoxin reductase-1 coincidental with the onset of cellular proliferation on day 120 after castration.
One or more of these genes may represent an appropriate target to prevent, delay or treat recurrent prostate cancer.
人前列腺癌异种移植瘤CWR22与大多数人前列腺癌相似，去势后会消退，并在去除雄激素数月后复发。通过比较在无雄激素状态下存在但增殖能力不同的肿瘤，鉴定出与增殖独特相关的基因。
比较来自20日龄去势小鼠的CWR22肿瘤（无法检测到增殖）和复发性CWR22肿瘤（增殖率与雄激素依赖性CWR22相似）的cDNA文库，以评估增殖是由功能获得还是抑制丧失触发的可能性。使用Northern印迹、Western印迹分析以及对一系列跨越从雄激素依赖性生长到复发生长转变的CWR22肿瘤进行免疫组织化学，进一步评估差异表达基因与细胞增殖开始的时间关联。
扣除杂交从1057个检测克隆中鉴定出11个候选基因。Northern印迹分析证实了8个基因的差异表达。Western印迹分析显示，肿瘤调节素、翻译延伸因子-1α（EF-1α）、Mxi-1和硫氧还蛋白结合蛋白2/维生素D上调蛋白与复发生长的开始之间存在关联。免疫组织化学显示，肿瘤调节素、EF-1α、Mxi-1和硫氧还蛋白还原酶-1的表达与去势后第120天细胞增殖的开始同时出现。
这些基因中的一个或多个可能是预防、延迟或治疗复发性前列腺癌的合适靶点。
