基于 KRAS 基因转导的大鼠胰腺癌模型中致癌蛋白表达的相似性与人胰腺癌相似。
Similarity of oncogenic protein expression in KRAS gene delivery-based rat pancreatic cancer model to that of human pancreatic cancer.
机构信息
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, 951-8510, Japan.
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, 951-8510, Japan; Department of General Medicine, Niigata University School of Medicine, Niigata, Niigata, 951-8510, Japan.
出版信息
Biochem Biophys Res Commun. 2023 Sep 17;673:29-35. doi: 10.1016/j.bbrc.2023.06.057. Epub 2023 Jun 17.
BACKGROUND
The development of effective therapies and biomarkers for pancreatic cancer is an unmet clinical need. To address this, we have developed an easy-to-use pancreatic cancer rat animal model via pancreas-targeted hydrodynamic gene delivery of human pancreatic cancer-related genes. Our study aimed to determine the molecular similarity between the pancreatic tumor in the rat model and human pancreatic cancer.
METHODS
KRAS gene-expressing plasmid was delivered to the pancreas of wild type rats via pancreas-targeted hydrodynamic gene delivery as previously reported. Tissue samples were collected at 5 weeks after the first gene delivery. The tumors developed in the rats were assessed for the expression of oncogenic proteins that are involved in human pancreatic cancer development.
RESULTS
The development of a tumor mimicking pancreatic ductal adenocarcinoma was confirmed. The expression levels of Cyclin D1, c-Jun, IL-33, and Zip4 proteins in the tumor were immunohistochemically assessed and the correlation of the proteins was confirmed. The expression pattern showed similarity to that of surgically resected human pancreatic cancer tissues.
CONCLUSIONS
Our study findings showing a similar pattern of oncogenic protein expression in novel KRAS gene-induced rat pancreatic cancer model and human pancreatic cancer will be useful for establishing novel tumor markers and therapeutic options for pancreatic cancer.
背景
开发有效的治疗方法和生物标志物来治疗胰腺癌是一个未满足的临床需求。为了解决这个问题，我们通过胰腺靶向水力基因传递人类胰腺癌相关基因，开发了一种易于使用的胰腺癌大鼠动物模型。我们的研究旨在确定大鼠模型中的胰腺肿瘤与人类胰腺癌之间的分子相似性。
方法
如前所述，通过胰腺靶向水力基因传递将表达 KRAS 基因的质粒递送到野生型大鼠的胰腺中。在第一次基因传递后 5 周收集组织样本。评估大鼠中肿瘤的致癌蛋白表达，这些蛋白参与人类胰腺癌的发生。
结果
证实了一种模拟胰腺导管腺癌的肿瘤的发展。通过免疫组织化学评估肿瘤中细胞周期蛋白 D1、c-Jun、IL-33 和 Zip4 蛋白的表达水平，并证实了这些蛋白之间的相关性。表达模式与手术切除的人类胰腺癌组织相似。
结论
我们的研究结果表明，新型 KRAS 基因诱导的大鼠胰腺癌模型和人类胰腺癌中致癌蛋白表达具有相似的模式，这将有助于建立新型的胰腺癌肿瘤标志物和治疗选择。
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