Coexpression of IGF-1R and c-Src proteins in human pancreatic ductal adenocarcinoma.
Aberrant c-Src protein kinase activation has been identified as one of the molecular alterations involved in human pancreatic carcinogenesis. It has been postulated that c-Src may induce transformation by causing the overexpression of the insulinlike growth factor-1 receptor (IGF-1R) in pancreatic tumor cell lines. To further study the interaction between c-Src and IGF-1R proteins in human pancreatic cancer, we examined their coexpression in 47 human pancreatic ductal adenocarcinomas (PDA). Formalin-fixed, paraffin-embedded sections from 47 cases of PDA were stained using the immunohistochemical avidin-biotin-peroxidase method. We used an anti-human IGF-1R mouse monoclonal antibody (dilution 1:100 with antigen retrieval), and an anti-c-Src mouse monoclonal antibody (dilution 1:100 with antigen retrieval). The stains were semiquantitatively evaluated using the Allred score system, assessing intensity of stain and percentage of positive tumor cells. High cytoplasmic c-Src expression (Allred score 7-8) was seen in 33/47 (70%) tumors. In only 4 cases was c-Src either negative or low (Allred score 3). Strong and diffuse membranous IGF-1R stain (Allred score 7-8) was identified in 30/47 (64%) tumors. IGF-1R staining was low (Alled score 2-4) in 2 cases and negative in 1. Interestingly, in 40/47 (85%) cases c-Src and IGF-1R stains had similar scores. An inverse staining pattern was detected in only 6/47 (13%) tumors. Normal pancreatic ducts as well as areas of chronic pancreatitis were negative for IGF-1R. In conclusion, our data support the role of IGF-1R and c-Src in human pancreatic carcinogenesis; the coexpression of both these molecules may play an important role in transformation of pancreatic ductal cells.
Hakam
Ardeshir
A
Department of Interdisciplinary Oncology , Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612-9497, USA.
Fang
Quan
Q
Karl
Richard
R
Coppola
Domenico
D
D000328:Adult; D000368:Aged; D000081247:CSK Tyrosine-Protein Kinase; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D016019:Survival Analysis; D019061:src-Family Kinases
D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human