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HIF1 alpha isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation

Monsef, N; Soller, M; Panagopoulos, I; Abrahamsson, PA; (2010) HIF1 alpha isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation. BMC Cancer , 10 , Article 385. 10.1186/1471-2407-10-385. Green open access

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Abstract

Background: Neuroendocrine (NE) differentiation in prostate cancer has been correlated with a poor prognosis and hormone refractory disease. In a previous report, we demonstrated the presence of immunoreactive cytoplasmic hypoxia inducible factor 1 alpha (HIF1 alpha), in both benign and malignant NE prostate cells. HIF1 alpha and HIF1 beta are two subunits of HIF1, a transcription factor important for angiogenesis. The aim of this study was to elucidate whether the cytoplasmic stabilization of HIF1 alpha in androgen independent NE differentiated prostate cancer is due to the presence of certain HIF1 alpha isoforms.Methods: We studied the HIF1 alpha isoforms present in 8 cases of benign prostate hyperplasia (BPH) and 43 cases of prostate cancer with and without NE differentiation using RT-PCR, sequencing analysis, immunohistochemistry and in situ hybridization.Results: We identified multiple isoforms in both benign and malignant prostate tissues. One of these isoforms, HIF1 alpha 1.2, which was previously reported to be testis specific, was found in 86% of NE-differentiated prostate tumors, 92% of HIF1 alpha immunoreactive prostate tumors and 100% of cases of benign prostate hyperplasia. Immunohistochemistry and in situ hybridization results showed that this isoform corresponds to the cytoplasmic HIF1 alpha present in androgen-independent NE cells of benign and malignant prostate tissue and co-localizes with immunoreactive cytoplasmic HIF1 beta.Conclusion: Our results indicate that the cytoplasmic stabilization of HIF1 alpha in NE-differentiated cells in benign and malignant prostate tissue is due to presence of an HIF1 alpha isoform, HIF1 alpha 1.2. Co-localization of this isoform with HIF1 beta indicates that the HIF1 alpha 1.2 isoform might sequester HIF1 beta in the cytoplasm.

Type: Article
Title: HIF1 alpha isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-2407-10-385
Publisher version: http://dx.doi.org/10.1186/1471-2407-10-385
Language: English
Additional information: © 2010 Monsef et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HYPOXIA-INDUCIBLE FACTOR-1-ALPHA, ENDOTHELIAL GROWTH-FACTOR, DOMINANT-NEGATIVE ISOFORM, CANCER-CELLS, ANDROGEN RECEPTOR, FACTOR-LOT, VEGF-C, EXPRESSION, PROLIFERATION, HIF-1-ALPHA
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1313300
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