Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D

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-rasG12D 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-rasG12D 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.

Overexpressed integrin alpha 2 inhibits the activation of the transforming growth factor β pathway in pancreatic cancer via the TFCP2-SMAD2 axis

“…KRAS is one of the main driving genes in pancreatic cancer. More than 90% of pancreatic cancer patients have KRAS carcinogenic point mutations, which constitutively activate the RAS signaling pathway [ 12 – 14 ]. The RAS signal transduction regulates multiple cellular biological processes in the pancreatic ductal adenocarcinoma, including the proliferation, migration, metabolism, and autophagy of the cells [ 15 ].…”

Overexpressed Integrin Alpha 2 Inhibits the Activation of the Transforming Growth Factor β Pathway in Pancreatic Cancer via the TFCP2-SMAD2 Axis

“…KRAS is one of the main driving genes in pancreatic cancer. More than 90% of patients with pancreatic cancer have KRAS carcinogenic point mutations, which result in the constitutive activation of the RAS signaling pathway [12][13][14]. RAS signal transduction regulates multiple cellular biological processes in pancreatic ductal adenocarcinoma, including cell proliferation, migration, metabolism, and autophagy [15].…”