Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues
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 in the epithelial du...
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Veröffentlicht in: | International journal of molecular medicine 2008-10, Vol.22 (4), p.421-431 |
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Zusammenfassung: | 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 in the epithelial ducts of normal
breast and breast cancer tissue. 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. Applying the four IDE-directed antibodies, we demonstrated IDE expression
at the protein level, by means of immunoblotting and immunocytochemistry, in each
of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression
was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal
muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization
of IDE indicated cytoplasmic localization of IDE in each of the cell lines and
tissues assessed. In conclusion, we performed for the first time a wide-ranging
survey on IDE protein expression in normal and malignant tissues and cells thus
extending our knowledge on the cellular and tissue distribution of IDE, an enzyme
which to date has mainly been studied in connection with Alzheimer's disease and
diabetes but not in cancer. |
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ISSN: | 1107-3756 |
DOI: | 10.3892/ijmm_00000038 |