Differential expression of gp200-MR6 molecule in benign hyperplasia and down-regulation in invasive carcinoma of the breast

Abstract

Summary In this study, we used immunohistochemical and biochemical analysis to show that gp200-MR6, a 200 kDa molecule that is functionally associated with the human interleukin 4 (IL-4) receptor complex, is expressed at high levels on normal breast epithelial tissues, at lower levels on in situ carcinomas, and that the expression is lost in the invasive carcinoma of the breast. Furthermore, a preliminary study showed that benign epithelial hyperplasia of the breast expresses the gp200-MR6 heterogeneously. Two populations of cells have been observed: MR6 positive and MR6 negative. Interestingly, MR6-positive cells were observed to have different morphology from those that were MR6 negative; the nuclei of the former were larger and rounded in shape, whereas the nuclei of the latter were relatively small and oval in shape. In sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, monoclonal antibody MR6 detects the same molecular weight molecule in both normal and transformed tissue, indicating that the molecule is not a product of a truncated gene. The intensity of the gp200-MR6 bands correlates with the immunohistochemical data, indicating that the molecule is expressed at high levels in normal tissue and at lower levels in malignant tissue. These results suggest that analysis of gp200-MR6 expression may be useful in tumour grading and prognostic evaluation in breast cancer. Moreover, the molecule may be involved early in the process of tumorigenesis of the breast, in which a loss or a down-regulation of gp200-MR6 could contribute towards tumour development and progression via an effect on cell growth and differentiation.

Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205–DCL‐1 fusion protein upon dendritic cell maturation

“…CD205 (protein and mRNA) was also detected on B cells, natural killer (NK) cells, neutrophils, eosinophils and all intestinal epithelial cell lines tested, but was not detectable in human sapheous vein endothelial cells (data not shown). This distribution corresponds with, and extends, published data 11,27 , 28 …”

Inhibition of growth and enhancement of differentiation of colorectal carcinoma cell lines by MAb MR6 and IL-4

“…From these findings, together with our previous observations that gp200-MR6 expression is lost from invasive carcinoma while strongly expressed on normal epithelial tissue of the breast (Al-Tubuly et al, 1996), it is tempting to speculate that gp200-MR6 might be a product of a tumour suppressor gene and that malignant transformation of epithelial cells is associated with the loss of this molecule. The use of the gp200-MR6 gene, which is currently being cloned in our laboratory, would facilitate further genetic studies such as loss of heterozygosity analysis and genetransfection studies which would confirm the possible tumour suppressor function of the gp200-MR6 molecule.…”

“…In contrast, IL-4 has been shown to have a growth inhibitory effect on human colon, renal and breast carcinoma cell lines, (Toi et al, 1992;Obiri et al, 1993;Lahm et al, 1994). Using immunohistochemical and biochemical analysis (Al-Tubuly et al, 1996) for a range of breast tissues, we have demonstrated that gp200-MR6 is weakly expressed on carcinoma in situ and lost on invasive tumours of the breast, while it is strongly expressed on the normal counterparts of the same tissue. Previous preliminary studies have also shown similar loss of gp200-MR6 expression with increased malignancy in colorectal carcinomas (Brady, 1994).…”

Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: Identification of interleukin‐8 as a potential regulatory factor in breast tumours

“…IL-4 was detected in only a small number of samples from both tissue populations, even though the IL-4 receptor appears to be elevated in breast tumours (Al-Jabaari et al, 1989) and recently gp200-MR6, a 200 kDa molecule which is functionally associated with the IL-4 receptor, has been shown to be differentially expressed in breast carcinomas (Al-Tubuly et al, 1996). Further, breast cancer cell lines respond to IL-4 in a non-autocrine manner (Toi et al, 1992).…”