Brändström A, Westin P, Bergh A, Cajander S, Damber J E
Department of Urology and Andrology, University of Umeå, Sweden.
Cancer Res. 1994 Jul 1;54(13):3594-601.
Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate. The mRNA expression of testosterone repressed prostatic message-2 and tissue-type plasminogen activator in the Dunning tumor and in the ventral prostate was analyzed by Northern blot experiments and immunohistochemical procedures. The degree of endonuclease-degraded genomic DNA was examined by gel electrophoresis. Apoptotic tumor epithelial cells were identified with in situ end labeling. Epithelial cells incorporating bromodeoxyuridine (BrdUrd) after castration in the ventral prostate and the Dunning tumors were localized with immunostaining. Androgen ablation resulted in an induction of testosterone repressed prostatic message-2 and tissue-type plasminogen activator transcripts in the normal prostate with a peak at approximately 2 to 5 days post castration. These transcript levels in the Dunning prostatic tumors did not show any induction during the same period. Immunohistochemical staining for sulfated glycoprotein-2 and tissue-type plasminogen activator confirmed this difference between the tumor tissue and the ventral prostate at the transcriptional level. The determination of DNA integrity showed similar results in that the degree of DNA fragmentation in the tumor was much lower than the initial and marked degradation of DNA in the ventral prostate. The number of in situ end-labeled epithelial tumor cells were not increased by castration. BrdUrd immunodetection showed that castration induced an initial increase in the number of BrdUrd-positive epithelial cells in the ventral prostate. In the tumors, castration resulted in a decrease in BrdUrd-positive epithelial cells. It was concluded that in the androgen-sensitive prostatic Dunning R3327 PAP adenocarcinoma, the biochemical cascade leading to apoptosis is not activated by androgen withdrawal, as in the ventral prostate.
在14天的去势后期间，对雄激素敏感的邓宁R3327 PAP前列腺腺癌中的细胞凋亡进行了研究，并与腹侧前列腺进行了比较。通过Northern印迹实验和免疫组织化学方法分析了邓宁肿瘤和腹侧前列腺中睾酮抑制的前列腺信息-2和组织型纤溶酶原激活剂的mRNA表达。通过凝胶电泳检查核酸内切酶降解的基因组DNA的程度。用原位末端标记鉴定凋亡的肿瘤上皮细胞。用免疫染色定位去势后腹侧前列腺和邓宁肿瘤中掺入溴脱氧尿苷（BrdUrd）的上皮细胞。雄激素去除导致正常前列腺中睾酮抑制的前列腺信息-2和组织型纤溶酶原激活剂转录物的诱导，在去势后约2至5天达到峰值。在同一时期，邓宁前列腺肿瘤中的这些转录水平没有显示出任何诱导。硫酸化糖蛋白-2和组织型纤溶酶原激活剂的免疫组织化学染色在转录水平上证实了肿瘤组织和腹侧前列腺之间的这种差异。DNA完整性的测定显示了类似的结果，即肿瘤中DNA片段化的程度远低于腹侧前列腺中DNA的初始和明显降解。去势并未增加原位末端标记的上皮肿瘤细胞的数量。BrdUrd免疫检测显示，去势诱导腹侧前列腺中BrdUrd阳性上皮细胞数量最初增加。在肿瘤中，去势导致BrdUrd阳性上皮细胞减少。得出的结论是，在雄激素敏感的前列腺邓宁R3327 PAP腺癌中，导致细胞凋亡的生化级联反应不像在腹侧前列腺中那样被雄激素剥夺激活。
