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PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation
Author(s) -
Lang Deborah,
Mascarenhas Joseph B.,
Powell Sara K.,
Halegoua Jason,
Nelson Maria,
Ruggeri Bruce A.
Publication year - 2008
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20375
Subject(s) - biology , stem cell , pancreas , cellular differentiation , cancer research , pax6 , downregulation and upregulation , cancer stem cell , pancreatic cancer , stem cell marker , microbiology and biotechnology , cd44 , transcription factor , cell , cancer , endocrinology , genetics , gene
Tumors of the exocrine pancreas are a major cause of cancer death and have among the poorest prognosis of any malignancy. Following the “cancer stem cell hypothesis,” where tumors are believed to originate in tissue specific stem cells, we screened primary ductal pancreatic carcinomas and cell lines for the expression of possible stem cell factors. We find 32/46 (70%) of primary tumors and 9/10 (90%) of cell lines express PAX6. PAX6 is a transcription factor expressed throughout the pancreatic bud during embryogenesis but not in the mature exocrine pancreas. PAX proteins have also been implicated in maintaining stem cells in a committed but undifferentiated state but a role for PAX proteins in putative pancreas stem cells is not known. We induced a pancreatic carcinoma cell line, Panc‐1, to differentiate by transfecting wild‐type p53 and treating the cells with differentiation agents gastrin or butyrate. This treatment induces cells to terminally differentiate into a growth‐arrested cell with neurite‐like processes, express the terminal differentiation marker somatostatin and downregulate PAX6. This phenotype can be replicated by directly inhibiting PAX6 expression. These data support a model where PAX proteins are aberrantly expressed in tumors and downregulation leads to differentiation. © 2007 Wiley‐Liss, Inc.