scholarly journals c-Fos/ERK promotes the progression from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma

2016 ◽  
Vol 36 (6) ◽  
pp. 3413-3420 ◽  
Author(s):  
Lei You ◽  
Xiaoxia Ren ◽  
Yongxing Du ◽  
Wenjing Zhao ◽  
Ming Cui ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Intraepithelial Neoplasia

scholarly journals Acinar transformed ductal cells exhibit differential mucin expression in a tamoxifen-induced pancreatic ductal adenocarcinoma mouse model

Biology Open ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. bio052878
Author(s):  
Kavita Mallya ◽  
Dhanya Haridas ◽  
Parthasarathy Seshacharyulu ◽  
Ramesh Pothuraju ◽  
Wade M. Junker ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Chemotherapy Response ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Ductal Cells ◽  
Mucin Expression ◽  
Acinar To Ductal Metaplasia

ABSTRACTPancreatic cancer (PC) is acquired postnatally; to mimic this scenario, we developed an inducible KrasG12D; Ptf1a-CreER™ (iKC) mouse model, in which Kras is activated postnatally at week 16 upon tamoxifen (TAM) administration. Upon TAM treatment, iKC mice develop pancreatic intraepithelial neoplasia (PanIN) lesions and PC with metastasis at the fourth and fortieth weeks, respectively, and exhibited acinar-to-ductal metaplasia (ADM) and transdifferentiation. Kras activation upregulated the transcription factors Ncoa3, p-cJun and FoxM1, which in turn upregulated expression of transmembrane mucins (Muc1, Muc4 and Muc16) and secretory mucin (Muc5Ac). Interestingly, knockdown of KrasG12D in multiple PC cell lines resulted in downregulation of MUC1, MUC4, MUC5AC and MUC16. In addition, iKC mice exhibited ADM and transdifferentiation. Our results show that the iKC mouse more closely mimics human PC development and can be used to investigate pancreatic ductal adenocarcinoma (PDAC) biomarkers, early onset of PDAC, and ADM. The iKC model can also be used for preclinical strategies such as targeting mucin axis alone or in combination with neo-adjuvant, immunotherapeutic approaches and to monitor chemotherapy response.

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