Insulin-like growth factor 1 receptors in human breast tumour: Localisation and quantification by histo-autoradiographic analysis

Abstract

To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on frozen tissue sections and analysed using 3H Ultrofilm autoradiography coupled to computerised image analysis. Competitive binding experiments using unlabelled IGF1, IGF2 and insulin showed that the tissues exhibited typical type I IGF binding sites. This specificity was confirmed by the use of alpha IR-3 monoclonal antibody, as inhibitor of 125I-IGF1 binding. IGF1 binding sites were detected in 18 human primary breast cancers, 12 benign breast tumours and two normal breast tissues. Using HAA we found that the human breast carcinomas studied exhibit a specific and high binding capacity for 125I-IGF1 exclusively localised on the proliferative epithelial component. The 125I-IGF1 binding activity of benign breast tumours or normal breast tissue was significantly lower than in cancerous tissues. There was a significant correlation between IGF1-R concentrations detected with HAA and those detected with a classical biochemical method. Moreover, HAA could be useful in further detailing whether a tumour is IGF1-R positive or negative HAA appears to be a useful method for the detection of growth factor receptors, specially in small biopsy specimens. Images Figure 2 Figure 3

Type I insulin-like growth factor receptor gene expression in normal human breast tissue treated with oestrogen and progesterone

“…In the present study, we have not quantified the changes in cell surface IGFR-I concentrations. However, using ['25I]IGF-I hisoautoradiography (Jammes et al, 1992), we confirmed that the IGFR-I is expressed solely on the epithelial component of xenografted normal human breast tissue (data not shown). Although the IGFR-I mRNA levels measured by RT-PCR could be affected by changes in the ratio of epithelial to stromal cells in the xenografts, no change to this ratio in response to ovarian steroid administration was observed as assessed by histological examination of the xenografts (Laidlaw et al, 1995).…”

“…In both normal and malignant human breast tissue, IGF-I and IGF-II mRNA are expressed by stromal fibroblasts, but generally not by the epithelium (Yee et al, 1989;Paik, 1992), whereas the expression of the IGFR-I is restricted to epithelial cells (Jammes et al, 1992). In vitro studies of the breast cancer cells have demonstrated that the IGFs are potent mitogens (Karey and Sirbasku, 1988), and that their growth-stimulatory effects can be blocked, both in vitro and in vivo, by a specific antibody (oIR-3) to the IGFR-I (Arteaga et al, 1989;Cullen et al, 1990).…”

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

“…6 Several studies have reported that IGF-IR levels are significantly higher in breast cancer tissue compared with normal breast tissue or benign tumors. [7][8][9] Patients with tumors containing a high IGF-IR gene copy number tend to have a shorter median overall survival than patients with tumors having a low amplified IGF-IR gene copy number. 10 Indeed, a recent study has shown that IGF-IR expression was 14-fold higher and that IGF-IR autophosphorylation and kinase activity were 2-to 4-fold higher in malignant breast tissue than in normal breast tissue.…”

Characterisation and location of insulin-like-growth factor (IGF) receptors in the foetal bovine Semitendinosus muscle

“…Most of the actions of IGFI and IGFII could be mediated by the type I receptor through auto/paracrine effects [14,37]. [23] and in adult muscular tissue [33]. Frozen sections (7 11 m) were processed as previously described [20].…”