Enhanced erbB-3 expression in human pancreatic cancer correlates with tumor progression.
The erbB-3 gene encodes a transmembrane protein that is related to the epidermal growth factor (EGF) receptor and erbB-2. We compared erbB-3 expression in the normal human pancreas, human pancreatic carcinomas, and cultured human pancreatic cancer cell lines. Northern blot analysis of total RNA revealed the anticipated 6.2-kb mRNA transcript in all 19 normal pancreatic samples. In 17 of 27 pancreatic cancers, there was a 6.7-fold increase (P < 0.001) in erbB-3 mRNA levels. Southern blot analysis did not reveal erbB-3 gene amplification. Four of six pancreatic cancer cell lines exhibited the 6.2-kb erbB-3 mRNA transcript, and all four cell lines coexpressed the epidermal growth factor receptor and erbB-2. Using a highly specific antibody, we determined that faint to moderate erbB-3 immunoreactivity was present in the ductal cells in the normal pancreas. In 47% (27/58) of the pancreatic cancers, there were many cancer cells with intense erbB-3 immunostaining. The presence of erbB-3 in the cancer cells was associated with advanced tumor stage and shorter survival postoperatively. These data indicate that a significant proportion of human pancreatic cancers overexpress erbB-3, and that erbB-3 may contribute to disease progression in this disorder.
Friess
H
H
Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Biological Chemistry, University of California, Irvine, California 92717, USA.
Yamanaka
Y
Y
Kobrin
M S
MS
Do
D A
DA
Büchler
M W
MW
Korc
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015139:Blotting, Southern; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D018815:Genes, erbB; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020893:Receptor, ErbB-3; D016019:Survival Analysis; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D066246:ErbB Receptors; D020893:Receptor, ErbB-3