Intratumoral IGF-I protein expression is selectively upregulated in breast cancer patients with BRCA1/2 mutations (2007)

Author(s): Hudelist G, Wagner T, Rosner M, Fink-Retter A, Gschwantler-Kaulich D, Czerwenka K, Kroiss R, Tea M, Pischinger K, Kostler WJ, Attems J, Mueller R, Blaukopf C, Kubista E, Hengstschlager M, Singer CF

    Abstract: BRCA1/2 mutations predispose to early onset breast and ovarian cancers. The phenotypic expression of mutant alleles, however, is thought to be modified by factors that are also involved in the pathogenesis of sporadic breast cancer. One such protein is IGF-I, one of the strongest mitogens to breast cancer cells in vitro. We have utilized immunohistochemistry to compare the intratumoral IGF-I and IGF-I receptor (IGF-IR) protein expression in 57 BRCA1/2 mutation carriers and 102 matched breast cancer patients without a family history in a nested case-control study. BRCA1 silencing by siRNA was used to investigate the effect of BRCA mutations on IGF-I protein expression. IGF-I protein expression was detected in tumoral epithelium and surrounding stroma, and was significantly upregulated in tumors of BRCA mutation carriers when compared with matched sporadic tumors (epithelial: 87.7% vs 61.8%, P=0.001; stromal: 73.7% vs 34.3%, P

      • Date: 01-12-2007
      • Journal: Endocrine-Related Cancer
      • Volume: 14
      • Issue: 4
      • Pages: 1053-1062
      • Publisher: Society for Endocrinology
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: BRCA1 Protein/*genetics BRCA2 Protein/*genetics Breast Neoplasms/*genetics/pathology Female *Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Heterozygote Detection Humans Insulin-Like Growth Factor I/*genetics *Mutation RNA, Small Interfering/genetics Receptor, IGF Type 1/genetics Transfection *Up-Regulation


      Professor Johannes Attems
      Professor of Neuropathology, Honorary Consultant Pathologist