DIFFERENTIAL EXPRESSION OF GP200-MR6 MOLECULE IN BENIGN HYPERPLASIA AND DOWN-REGULATION IN INVASIVE-CARCINOMA OF THE BREAST

In this study, we used immunohistochemical and biochemical analysis to show that gp200-MR6, a 200 kDa molecule that is functionally associat ed with the human interleukin 4 (IL-4) receptor complex, is expressed at high levels on normal breast epithelial tissues, at lower levels on ia situ carcinomas, and that the expression is lost in the invasive c arcinoma of the breast. Furthermore, a preliminary study showed that b enign epithelial hyperplasia of the breast expresses the gp200-MR6 het erogeneously. Two populations of cells have been observed: MR6 positiv e and MR6 negative. Interestingly, MR6-positive cells were observed to have different morphology from those that were MR6 negative; the nucl ei of the former were larger and rounded in shape, whereas the nuclei of the latter were relatively small and oval in shape. In sodium dodec yl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, monoclonal antibody MR6 detects the same molecular weight mo lecule in both normal and transformed tissue, indicating that the mole cule is not a product of a truncated gene. The intensity of the gp200- MR6 bands correlates with the immunohistochemical data, indicating tha t the molecule is expressed at high levels in normal tissue and at low er levels in malignant tissue. These results suggest that analysis of qp200-MR6 expression may be useful in tumour grading and prognostic ev aluation in breast cancer. Moreover, the molecule may be involved earl y in the process of tumorigenesis of the breast, in which a loss or a down-regulation of gp200-MR6 could contribute towards tumour developme nt and progression via an effect on cell growth and differentiation.