Table 2.
Development of Premalignant Lesions and PDAC From Varying Cells of Origin
| Mutation | Embryonic Expression |
Acinar Expression |
Ductal Expression |
|||
|---|---|---|---|---|---|---|
| Pathology | Cre Driver | Pathology | Cre Driver | Pathology | Cre Driver | |
| KrasG12D | PanIN/PDAC | Ptf1a-Cre32,50 Pdx1-Cre50 |
PanIN/late PDAC | Ptf1a-CreER57,86 | No lesions or cancer | Sox9-CreER57,86 |
| Early PanIN | CK19-CreERT258 | |||||
| Sporadic PanIN | Mist1-CreER56,87 Elastase-CreERT255,56 Dclk1-CreERT39 |
PDAC | Sox9-CreERT2 with PDL88 | |||
| PanIN | Elastase-CreERT2 with caerulein59 Mist1-CreER with caerulein87 Dclk1-CreERT with caerulein39 |
PDAC | CK19-CreERT2 with PDL88 | |||
| No lesions or cancer | Elastase-CreERTM with PDL88 | |||||
| sporadic PanIN | Pdx1-IRES-Cre21 Nestin-Cre53 |
|||||
| KrasG12V | PanIN/PDAC | Elas-tTA; tetO-Cre52 | No lesions or cancer | Elas-tTA; tetO-Cre52 | ||
| PanIN/PDAC | Elas-tTA; tetO-Cre with caerulein52 | |||||
| KrasG12D; p53R172H | PanIN/PDAC | Pdx1-Cre77 | PanIN/PDAC | Ptf1a-CreER86 Mist1-CreER89 |
No lesions or cancer | Hnf1b-CreERT289 |
| KrasG12D; p53flox/+ | PanIN/PDAC | Ptf1a-CreER86 | ||||
| KrasG12D; p53flox/flox | PanIN/PDAC | Pdx1-Cre80 | PanIN/PDAC | Ptf1a-CreER90,86 Elastase-CreERT2 with caerulein91 |
PDAC | Sox9-CreER90,86 |
| Nonmucinous tubular lesions/PDAC | CK19-CreER91 | |||||
| KrasG12D; p53flox/- or flox/R270H or flox/R172H | PanIN/PDAC | Ptf1a-CreER86 | PDAC | Sox9-CreER86 | ||
| KrasG12D; p53R172H/R172H | PDAC | Hnf1b-CreERT289 | ||||
| KrasG12V; p53+/– | PanIN/PDAC | Elas-tTA; tetO-Cre52 | ||||
| KrasG12D; p16–/– | PanIN/PDAC | Pdx1-Cre80,78 | ||||
| KrasG12D; p16/Arfflox/flox or –/– | PanIN/PDAC | Pdx1-Cre80,78 | ||||
| KrasG12D; Smad4flox/flox | IPMN/PDAC | Pdx1-Cre79 | ||||
| KrasG12D; Tgfbr2flox/flox | PanIN/PDAC | Ptf1a-Cre92 | ||||
| KrasG12V; p16/Arflox/+ | PanIN | Elas-tTA; tetO-Cre93 | ||||
| KrasG12V; p16/Arflox/lox | PanIN/PDAC | Elas-tTA; tetO-Cre93 | ||||
| KrasG12D; Lkb1lox/lox | PanIN/PDAC | Pdx1-Cre84 | IPMN/premature death | Sox9-CreERT272 | ||
| KrasG12D; Brg1f/f | IPMN/PDAC | Ptf1a-Cre68,70 | No lesions or cancer | Ptf1a–CreER68 | Few IPMN | Hnf1b-CreERT268 |
| KrasG12D; Arid1af/+ | PanIN | Ptf1a-Cre70 | PanIN | Ptf1a-CreERT2 with caerulein70 | No lesions or cancer | Hnf1b-CreERT270 |
| KrasG12D; Arid1af/f | PanIN and IPMN/PDAC | Ptf1a-Cre70 | PanIN | Ptf1a-CreERT2 with caerulein70 | Few IPMN | Hnf1b-CreERT270 |
| KrasG12D; Fbw7F/F | PanIN/PDAC | Elastase-CreERT2 with caerulein91 | Nonmucinous tubular lesions/PDAC | CK19-CreER91 | ||
| GNASR201H | Early IPMN | Ptf1a-Cre75 | ||||
| KrasG12D; GNASR201H | IPMN/cystic tumor | Ptf1a-Cre75 | ||||
| KrasG12D; GNASR201C | IPMN | Ptf1a-Cre76 | IPMN | Ptf1a-CreER76 | ||
| KrasG12D; GNASR201C; p53LoxP/+ | IPMN/PDAC | Ptf1a-CreER76 | ||||
| Ptenflox/flox | PanIN and papillary adenocarcinoma/PDAC | Pdx1-Cre94 | No lesions or cancer | Elastase-CreERTM94 | IPMN/PDAC—spontaneous Kras mutation | Sox9-CreERT271 |
| Ptenflox/flox; p53–/– | Papillary adenocarcinomas | Pdx1-Cre94 | ||||
| KrasG12D; Ptenflox/flox | IPMN/PDAC | Sox9-CreERT271 | ||||
Note: Blank cells indicate models that have not been evaluated.
ADM, acinar-ductal metaplasia; IPMN, intraductal papillary mucinous neoplasm; PanIN, pancreatic intraepithelial neoplasia; PDAC, pancreatic ductal adenocarcinoma; PDL, pancreatic duct ligation.