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CASTRATION THERAPY OF PROSTATE CANCER RESULTS IN DOWNREGULATION OF HIF-1 alpha LEVELS
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
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2012 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 82, no 3, 1243-1248 p.Article in journal (Refereed) Published
Abstract [en]

Background and Purpose: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. Methods and Materials: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in cancer was determined by immunofluorescence. Results: Among biopsy specimens taken before castration, strong HIF-1 alpha expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1 alpha (mean intensity 0-10) in 6 patients. Downregulation of HIF-1 alpha expression after castration was observed in all 5 patients with strong HIF-1 alpha precastration expression. HIF-1 alpha expression was also reduced in 2 of 3 patients with weak HIF-1 alpha precastration expression. Conclusions: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.

Place, publisher, year, edition, pages
2012. Vol. 82, no 3, 1243-1248 p.
Keyword [en]
Hypoxia-inducible factor, HIF-1 alpha, Prostate cancer
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-76984DOI: 10.1016/j.ijrobp.2011.10.038ISI: 000300423500064OAI: oai:DiVA.org:su-76984DiVA: diva2:530997
Note
5Available from: 2012-06-05 Created: 2012-05-28 Last updated: 2017-12-07Bibliographically approved

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