ENHANCED ERBB-3 EXPRESSION IN HUMAN PANCREATIC-CANCER CORRELATES WITHTUMOR 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 analys is of total RNA revealed the anticipated 6.2-kb mRNA transcript in all 19 normal pancreatic samples. In 17 of 27 pancreatic cancers, there w as a 6.7-fold increase (P < 0.001) in erbB-3 mRNA levels, Southern blo t analysis did not reveal erbB-3 gene amplification, Pour of six pancr eatic cancer cell lines exhibited the 6.2-kb erbB-3 mRNA transcript, a nd all four cell lines coexpressed the epidermal growth factor recepto r and erbB-2, Using a highly specific antibody, we determined that fai nt to moderate erbB-3 immunoreactivity was present in the ductal cells in the normal pancreas, In 47% (27/58) of the pancreatic cancers, the re were many cancer cells with intense erbB-3 immunostaining, The pres ence 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 disord er.