title: Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β-cell, regeneration.
abstract: The maternal embryonic leucine zipper kinase (MELK) is expressed in stem/progenitor cells in some adult tissues, where it has been implicated in diverse biological processes, including the control of cell proliferation. Here, we described studies on its role in adult pancreatic regeneration in response to injury induced by duct ligation and β-cell ablation. MELK expression was studied using transgenic mice expressing GFP under the control of the MELK promoter, and the role of MELK was studied using transgenic mice deleted in the MELK kinase domain. Pancreatic damage was initiated using duct ligation and chemical beta-cell ablation. By tracing MELK expression using a MELK promoter-GFP transgene, we determined that expression was extremely low in the normal pancreas. However, following duct ligation and β-cell ablation, it became highly expressed in pancreatic ductal cells while remaining weakly expressed in α-cells and β- cells. In a mutant mouse in which the MELK kinase domain was deleted, there was no effect on pancreatic development. There was no apparent effect on islet regeneration, either. However, following duct ligation there was a dramatic increase in the number of small ducts, but no change in the total number of duct cells or duct cell proliferation. In vitro studies indicated that this was likely due to a defect in cell migration. These results implicate MELK in the control of the response of the pancreas to injury, specifically controlling cell migration in normal and transformed pancreatic duct cells.
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Cheng-Ho
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Amber
authors.initials: A
authors.lastname: Miller
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Andreas
authors.initials: A
authors.lastname: Panopoulos
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Ergeng
authors.initials: E
authors.lastname: Hao
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Margolis
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Alexey
authors.initials: A
authors.lastname: Terskikh
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California.
authors.forename: Fred
authors.initials: F
authors.lastname: Levine
keywords: Cancer; MELK; duct; migration