A study of gene-expression profile in knock-in mouse prostate cancer model

1.为了研究一种新的转基因小鼠前列腺癌(KIMAP)模型的生物学特性，我们对KIMAP和转基因小鼠前列腺癌(TGMAP)模型进行了比较研究。(1)与TGMAP模型相比，KIMAP肿瘤表现出与人前列腺癌相似的异质性和多灶性。(2)基因芯片的比较研究表明，KIMAP肿瘤表达上调，免疫反应基因含量较高，而TGMAP肿瘤具有神经内分泌(NE)分化。(3)在KIMAP肿瘤中发现了几个具有人类前列腺癌特征的肿瘤标志物基因，包括Hepsin、maspin、Nkx3.1、Nkx3.1由于人前列腺癌与KIMAP肿瘤的相似性，这一临床前模型可能会补充现有的转基因模型以更准确地研究前列腺癌。为了探讨小鼠PSP94作为血清生物标志物在小鼠前列腺癌模型研究中的应用，我们用竞争性ELISA法测定了小鼠血清中PSP94的水平。与野生型小鼠相比，KIMAP小鼠血清PSP94水平随着肿瘤分级、肿瘤重量和年龄的增加而显著升高。通过对去势小鼠血清PSP94水平的纵向监测，我们发现反应性/难治性前列腺组织与血清PSP94水平之间存在相关性。证实了小鼠血清PSP94作为激素治疗标志物的实用性。我们在KIMAP模型中评估了带有精细超声探头的经直肠超声(TRUS)成像在测量前列腺癌进展方面的有用性。(1)30 MHz的扫描频率被发现是筛选小鼠前列腺癌的最佳方法。(2)TRUS成像可以识别最小直径为1.0 mm的肿瘤。(3)TRUS可以纵向观察小鼠前列腺癌的进展。

1. To study the biological characteristics of a new knock-in mouse adenocarcinoma of the prostate (KIMAP) model, we performed a comparative study with mice from both the KIMAP and transgenic mouse adenocarcinoma of the prostate (TGMAP) models.(1) The KIMAP tumors demonstrated a tumor architecture of heterogeneity and multifocality similar to that of human prostate cancer compared with TGMAP model.(2) Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas TGMAP tumors had neuroendocrine (NE) differentiation.(3) Several tumor marker genes characteristic of human prostate cancer were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.l, CD10 and PSP94, etc.Due to the similarities between human prostate cancers and the KIMAP tumors, this preclinical model may supplement the current transgenic models to study the prostate cancer more accurately.2. To investigate the use of mouse PSP94 as a serum biomarker for mouse prostate cancer model studies, we quantified PSP94 levels in the mouse serum with competitive ELISA techniques. Compared with wild-type mice, serum PSP94 levels increased significantly with tumor grade, tumor weight and age in KIMAP mice. Through longitudinal monitoring of serum PSP94 levels of castrated mice, we found a correlation between responsiveness/refractory prostate tissues and serumPSP94 levels. The utility of mouse serumPSP94 as a marker in hormone therapy was confirmed.3. We assessed the usefulness of transrectal ultrasonography (TRUS) imaging with a fine ultrasound probe for measuring prostate cancer progression in the KIMAP model.(1) A scanning frequency of 30 MHz was found to be best for screening of prostate cancer in mice.(2) TRUS imaging could identify tumors with a minimum size of 1.0 mm diameter.(3) TRUS allows a longitudinal observation of prostate cancer progression in mice.