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永生化小型猪胰腺癌细胞系表达致癌性 K-Ras 的建立和鉴定。

Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-Ras.

机构信息

Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si 28116, Korea.

Department of Biological Science, College of Natural Sciences, Wonkwang University, 460, Iksan-daero, Iksan-si 54538, Korea.

出版信息

Int J Mol Sci. 2020 Nov 21;21(22):8820. doi: 10.3390/ijms21228820.

Abstract

In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-ras regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-ras in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.

摘要

近几十年来,人们对胰腺癌的治疗和预防进行了许多研究。然而,胰腺癌仍然无法治愈,死亡率很高。尽管小鼠模型已被广泛用于临床前胰腺癌研究,但这些模型与人类有许多差异。因此,大型动物可能更有助于胰腺癌的研究。由于猪与人有相似之处,因此它们最近成为了一种新的胰腺癌模型,但尚未建立用于药物筛选或肿瘤生物学分析的猪胰腺癌细胞系。在这里,我们建立并鉴定了一种源自原代胰腺细胞和表达由人 PTF1A 启动子调控的 K-ras 的胰腺癌样细胞的永生化迷你猪胰腺细胞系。使用这种永生化细胞系,我们分析了与癌细胞特征相关的基因表达和表型。值得注意的是,我们发现由腺泡细胞构建的细胞系中 K-ras 导致了腺泡到导管的转分化。这可能构成了分析人类胰腺癌中腺泡到导管化生的良好研究模型。

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