title: Epidermal growth factor receptor expression in pancreatic lesions induced in the rat by azaserine.
abstract: In the present study, the expression of the epidermal growth factor receptor (EGFR) was investigated in putative preneoplastic and neoplastic acinar cell lesions induced in the rat pancreas by azaserine, using Northern blotting, in situ hybridisation (ISH) and immunohistochemistry. EGFR protein levels were decreased in putative preneoplastic eosinophilic acinar cell lesions (atypical acinar cell nodules, AACN) in comparison with normal acinar cells of the pancreas. However, EGFR mRNA expression correlated positively with the volume of AACN in pancreatic homogenates and ISH showed equal or stronger EGFR mRNA expression in AACN than in the surrounding normal acinar cells. Neither EGFR protein nor EGFR mRNA was detected in more advanced lesions such as acinar adenocarcinomas (in situ). Moreover, EGFR protein expression showed an inverse relationship with the mitotic rate of the acinar cells. These findings suggest that down-regulation of EGFR at the protein level may abrogate negative constraints on cell growth, which may stimulate the development of putative preneoplastic AACN to more advanced lesions and, ultimately, acinar adenocarcinomas.
authors.affiliation: TNO Nutrition and Food Research Institute, Department of Pathology, Zeist, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Visser
authors.forename: R A
authors.initials: RA
authors.lastname: de Weger
authors.forename: W T
authors.initials: WT
authors.lastname: van Blokland
authors.forename: I
authors.initials: I
authors.lastname: Seifert-Bock
authors.forename: M S
authors.initials: MS
authors.lastname: Kobrin
authors.forename: M
authors.initials: M
authors.lastname: Korc
authors.forename: R A
authors.initials: RA
authors.lastname: Woutersen
mesh_terms: D000818:Animals; D001377:Azaserine; D015152:Blotting, Northern; D002273:Carcinogens; D066246:ErbB Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009363:Neoplasm Proteins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000648:ultrastructure*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology / Q000648:ultrastructure*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D001377:Azaserine; D066246:ErbB Receptors