Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels

  • Authors:
    • Razvan T. Radulescu
    • Carla Hufnagel
    • Peter Luppa
    • Heide Hellebrand
    • Wen-Liang Kuo
    • Marsha Rich Rosner
    • Nadia Harbeck
    • Cecylia Giersig
    • Alfons Meindl
    • Manfred Schmitt
    • Gregor Weirich
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.73
  • Pages: 73-80
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Insulin is a hormone crucial to metabolism and an essential growth factor for normal and neoplastic tissues. We have now determined insulin in extracts of 23 primary breast cancer specimens and of non-neoplastic breast tissues by a chemiluminescent immunoassay. Remarkably, insulin was measured only in grade 3 tumors, whereas grade 2 carcinomas and the normal mammary gland were each insulin-negative. We also performed immunohistochemistry for insulin-degrading enzyme (IDE), a cytoplasmic zinc metalloprotease belonging to the inverzincin family and participating in insulin cleavage. IDE was detected in most insulin-positive grade 3 carcinomas, indicating that it might be dysfunctional in these anaplastic tumors. IDE was equally present in the insulin-negative grade 2 carcinomas. Moreover, five grade 3 carcinomas and one grade 2 carcinoma displayed a loss of heterozygosity in the 10q chromosomal region harboring the IDE gene, but, despite these alterations, IDE was detected immunohistochemically, indicating a retention of the second allele. Compared to the expression of IDE in 92% of the tumors examined, only 57% of 21 normal breast specimens stained positively for IDE. In contrast to this increase in IDE-positive epithelial cells in node-negative breast cancer vs. normal breast, additional immunohistochemical analysis of 17 node-positive breast carcinomas and corresponding tumor-bearing lymph nodes showed that IDE expression decreases from primary tumor to lymph node metastasis. Altogether, this study represents the first demonstration of IDE in normal and neoplastic human mammary tissues. Our present report should also provide an experimental starting point towards exploring a potential role of IDE in the control of tumor progression.

Related Articles

Journal Cover

January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Radulescu RT, Hufnagel C, Luppa P, Hellebrand H, Kuo W, Rosner MR, Harbeck N, Giersig C, Meindl A, Schmitt M, Schmitt M, et al: Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels. Int J Oncol 30: 73-80, 2007
APA
Radulescu, R.T., Hufnagel, C., Luppa, P., Hellebrand, H., Kuo, W., Rosner, M.R. ... Weirich, G. (2007). Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels. International Journal of Oncology, 30, 73-80. https://doi.org/10.3892/ijo.30.1.73
MLA
Radulescu, R. T., Hufnagel, C., Luppa, P., Hellebrand, H., Kuo, W., Rosner, M. R., Harbeck, N., Giersig, C., Meindl, A., Schmitt, M., Weirich, G."Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels". International Journal of Oncology 30.1 (2007): 73-80.
Chicago
Radulescu, R. T., Hufnagel, C., Luppa, P., Hellebrand, H., Kuo, W., Rosner, M. R., Harbeck, N., Giersig, C., Meindl, A., Schmitt, M., Weirich, G."Immunohistochemical demonstration of the zinc metalloprotease insulin-degrading enzyme in normal and malignant human breast: Correlation with tissue insulin levels". International Journal of Oncology 30, no. 1 (2007): 73-80. https://doi.org/10.3892/ijo.30.1.73