Changes in connexin43 expression and localization during pancreatic cancer progression.
Gap junctions and gap junction communication have long been recognized to play roles in tissue organization and remodeling through both cell autonomous and intercellular means. We hypothesized that these processes become dysregulated during pancreas cancer progression. Molecular and histological characterization of the gap junction protein, connexin43, during progression of pancreatic ductal adenocarcinoma could yield insight into how these events may contribute to or be modulated during carcinogenesis. In a mouse model of pancreatic ductal adenocarcinoma generated through targeted endogenous expression of Kras(G12D) in the murine pancreas, we examined the evolving expression and localization of connexin43. Overall, connexin43 expression increased over time, and its localization became more widespread. At early stages, connexin43 is found almost exclusively in association with the basolateral membrane of duct cells found in invasive lesions. Connexin43 became increasingly associated with the surrounding stroma over time. Connexin43 phosphorylation was also altered during tumorigenesis, as assessed by migrational changes of the protein in immunoblots. These data suggest a potential role for gap junctions and connexin43 in mediating interactions between and amongst the stromal and epithelial cells in pancreatic ductal adenocarcinoma.
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M5C800, Box 19024, Seattle, WA 98109, USA.
Joell L
JL
Solan
Sunil R
SR
Hingorani
Paul D
PD
Lampe
D000818:Animals; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D018031:Connexin 43 / Q000378:metabolism*; D018450:Disease Progression; D017629:Gap Junctions / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation
D018031:Connexin 43