Localization of immunoreactive HIF-1alpha and HIF-2alpha in neuroendocrine cells of both benign and malignant prostate glands.
Författare
Summary, in English
BACKGROUND. Hypoxia induces increased tumor growth by promoting angiogenic and glycolytic pathways. Tumors expressing hypoxia-inducible factor-la (HIF-1 alpha), an important transcriptional activator of oxygen-regulated genes, are resistant to chemotherapy and radiotherapy. The major challenge in prostate cancer therapy today is to gain a better understanding of the development of hormone-refractory tumors, which is often characterized by neuroendocrine differentiation. Here we studied the expression of HIF-1 alpha and HIF-2 alpha in neuroendocrine cells of the benign prostate and in prostate cancer. METHODS. Tissue sections from 30 patients who underwent radical prostatectomy and from 21 patients operated by transurethral resection of the prostate were selected for immunohistochemical analysis for expression of HIF-l a, HIF-2a, androgen receptor (AR), neuroendocrine markers (chromogranin A, synaptophysin), and two gene products downstream of HIF-1a: VEGF and GAPDH. RESULTS. Immunoreactive HIF-1 alpha was detected in a subpopulation of AR-negative neuroendocrine cells in benign and malignant prostate tissue. Analysis of serial sections showed that the levels of expression of GAPDH and VEGF proteins are increased in AR-negative malignant neuroendocrine cells expressing HIF-1 alpha. in situ-hybridization indicated that HIF-1 alpha mRNA levels are not higher in neuroendocrine prostate cancer cells relative to corresponding non-neuroendocrine tumor cells. We also demonstrated induced stabilization of nuclear HIF-1 alpha in LNCaP cells by hypoxia and long-term stimulation with interleukin-6. Focal HIF-2 expression was detected in benign neuroendocrine-like cells and in malignant prostatic cells. CONCLUSIONS. The expression of HIF-1 alpha and HIF-2a in prostate cancer has been confirmed, but we also identified immunoreactive HIF-1 alpha and downstream gene products in benign and malignant prostate neuroendocrine cells. Prostate 67:1219-1229, 2007, (c) 2007 Wiley-Liss, Inc.
Publiceringsår
2007
Språk
Engelska
Sidor
1219-1229
Publikation/Tidskrift/Serie
The Prostate
Volym
67
Issue
11
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Obstetrics, Gynecology and Reproductive Medicine
Status
Published
Forskningsgrupp
- Pathology, Malmö
- Clinical Chemistry, Malmö
ISBN/ISSN/Övrigt
- ISSN: 0270-4137