Expression of metalloprotease insulin-degrading enzyme (insulysin) in breast and ovarian cancer tissues

Background. Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated for the first time in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30: 73; 2007). Materials and Methods. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results. Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast, ovary, and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed, including breast and ovarian cancer. Conclusions. We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer disease and diabetes but not in cancer.

Insulin-degrading enzyme (IDE) - breast cancer - normal human tissues - ovarian cancer - tumor cell lines