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Coexpression of IGF-1R and c-Src Proteins in Human Pancreatic Ductal Adenocarcinoma

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Abstract

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.

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Authors and Affiliations

  1. Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute and University of South Florida Tampa, Florida, USA

    Ardeshir Hakam, Quan Fang & Domenico Coppola

  2. Department of Pathology, Moffitt Cancer Center and Research Institute and University of South Florida Tampa, Florida, USA

    Ardeshir Hakam & Domenico Coppola

  3. Department of Surgery, Moffitt Cancer Center and Research Institute and University of South Florida Tampa, Florida, USA

    Richard Karl

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  1. Ardeshir Hakam
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  4. Domenico Coppola
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Hakam, A., Fang, Q., Karl, R. et al. Coexpression of IGF-1R and c-Src Proteins in Human Pancreatic Ductal Adenocarcinoma. Dig Dis Sci 48, 1972–1978 (2003). https://doi.org/10.1023/A:1026122421369

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