Establishment of an invasive prostate cancer model in transgenic rats by intermittent testosterone administration.
Establishment of an invasive prostate cancer model in transgenic rats by intermittent testosterone administration.
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DOI：
10.1293/tox.2013-0052
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发表时间：
2014-04
影响因子：
1.2
通讯作者：
Takahashi S
中科院分区：
文献类型：
--
作者：
Sato S;Suzuki S;Naiki-Ito A;Komiya M;Ne L;Kato H;Sagawa H;Yamashita Y;Shirai T;Takahashi S
我们建立了一种前列腺腺癌转基因大鼠（TRAP）模型，其特点是在较短的实验时间内，前列腺叶腺癌以高发病率均匀发展。然而，没有观察到具有与人类相似的反应性基质特征的浸润性癌。因此，我们专注于利用TRAP大鼠建立一种新的侵袭性前列腺癌模型。实验1,1、2组雄性TRAP大鼠在实验第0天切除睾丸。1 ~ 3组大鼠分别于第1 ~ 4周和第6 ~ 16周植入丙酸睾酮（TP）。1、3组大鼠植入术后给予3,2′-二甲基-4-氨基联苯（DMAB）。第4组大鼠为对照组。实验2将大鼠分为三组，均不接受DMAB或睾丸切除术，连续给予TP治疗或停药1次或2次。实验1在前列腺背外侧和前部发现浸润性腺癌伴丰富的胶原基质，部分在16周时表现为浸润周围神经间隙。3组浸润性癌灶数量最多。在实验2中，前列腺外侧浸润性腺癌的发展与TP给药/停药周期的次数相关。总之，我们新建立的前列腺浸润性腺癌大鼠模型可作为评估靶向肿瘤微环境的预防和治疗药物在体内疗效的有用临床前模型。
We have established a transgenic rat for adenocarcinoma of the prostate (TRAP) model that features uniform adenocarcinoma development in prostatic lobes at high incidence within a short experimental period. However, no invasive carcinomas with reactive stroma characteristics similar to those in man were observed. We therefore have focused on a new model for invasive carcinoma of the prostate using TRAP rats. In experiment 1, male TRAP rats in groups 1 and 2 were treated with orchiectomy at day 0 of the experiment. Rats in groups 1–3 underwent testosterone propionate (TP) implantation from weeks 1 to 4 and from weeks 6 to 16. Rats in groups 1 and 3 were given 3,2’-dimethyl-4-aminobiphenyl (DMAB) after TP implantation. The rats of group 4 served as controls. In experiment 2, the rats were divided into three groups, none of which received DMAB or orchiectomy, treated with TP continuously or with the treatment withdrawn once or twice. In experiment 1, invasive adenocarcinomas with abundant collagenous stroma were found in the dorsolateral and anterior prostate, some of which showed perineural space invasion at week 16. The number of invasive carcinoma foci was most frequent in group 3. In experiment 2, invasive adenocarcinoma development in the lateral prostates was correlated with the number of TP administration/withdrawal cycles. In conclusion, our newly established rat model for invasive adenocarcinoma of the prostate could serve as a useful preclinical model for evaluating the in vivo efficacy of preventive and therapeutic agents targeting of the tumor microenvironment.
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作者：
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通讯作者：
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作者：
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