Evaluation of NKX3.1 and C-MYC expression in canine prostatic cancer
Evaluation of NKX3.1 and C-MYC expression in canine prostatic cancer
复制标题
DOI：
10.1016/j.rvsc.2018.04.001
复制
发表时间：
2018-06-01
影响因子：
2.4
通讯作者：
Laufer-Amorim, Renee
中科院分区：
文献类型：
--
作者：
Fonseca-Alves, Carlos Eduardo;Kobayashi, Priscila Emiko;Laufer-Amorim, Renee
NKX3.1/C-MYC交叉调节在正常人前列腺中已有报道，NKX3.1的丢失和C-MYC的获得似乎是前列腺癌发展和进展中的重要事件。狗可以成为人类前列腺疾病的有趣模型，但只有一项先前的研究表明犬前列腺中NKX3.1和MYC的失调。为了研究NKX3.1和C-MYC在犬前列腺病变组织中的表达，本研究检测了NKX3.1和C-MYC在犬正常前列腺组织中的基因和蛋白表达。我们确定了一个26 kDa的条带，对应于NKX3.1蛋白，而C-MYC显示了一个50 kDa的条带的蛋白质印迹分析的所有前列腺组织。我们观察到，NKX3.1蛋白和转录在前列腺癌（PC）样品相比，非肿瘤样品下调。我们还观察到，与正常（P=.001）和增生性炎性萎缩（PIA）样本（P=.003）相比，PC样本中C-MYC蛋白过表达。我们发现NKX3.1和C-MYC蛋白在正常和PIA样本中的表达呈正相关。有趣的是，在PC中观察到NKX3.1和MYC转录物之间的负相关性（NKX3.1下调和MYC过表达）。因此，具有较高C-MYC表达的样品也表现出较高的NKX3.1表达，这表明NKX3.1蛋白对C-MYC的调节。与人类一样，这两种基因和蛋白质被发现与犬前列腺癌有关。然而，与在人类中观察到的相反，在犬PC样品中，NKX3.1的下调不能通过DNA超甲基化来解释。
NKX3.1/C-MYC cross-regulation has been reported in the normal human prostate, and loss of NKX3.1 and gain of C-MYC seem to be important events in prostate cancer development and progression. The dog can be an interesting model for human prostatic disease, and yet only one previous research study has shown deregulation of NKX3.1 and MYC in the canine prostate. To address the expression of NKX3.1 and C-MYC in different canine prostatic lesions, this study verified the gene and protein expression of NKX3.1 and C-MYC in normal canine prostatic tissues. We identified a 26 kDa band that corresponded to the NKX3.1 protein, while C-MYC showed a 50 kDa band on Western blotting analysis of all prostatic tissues. We observed that NKX3.1 protein and transcript were down-regulated in prostate cancer (PC) samples compared with non-neoplastic samples. We also observed that C-MYC protein was overexpressed in PC samples compared with normal (P=.001) and proliferative inflammatory atrophy (PIA) samples (P=.003). We found a positive correlation between NKX3.1 and C-MYC protein expression in normal and PIA samples. Interestingly, a negative correlation (NKX3.1 downregulation and MYC overexpression) was observed between NKX3.1 and MYC transcripts in PC. Thus, samples with higher C-MYC expression also exhibited higher NKX3.1 expression, which indicates the regulation of C-MYC by NKX3.1 protein. As in humans, these two genes and proteins were found to be related to canine prostate cancer. However, in contrast from what is observed in humans, in canine PC samples, the downregulation of NKX3.1 cannot be explained by DNA hypermethylation.