HIF1α isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation

BMC Cancer

Research Article

Maria Soller¹  Ioannis Panagopoulos¹  Per Anders Abrahamsson²  Nastaran Monsef³ 

[1] Department of Clinical Genetics, Lund University Hospital, Sweden;Department of Clinical Sciences, Division of Urological Cancer, Malmö University Hospital, Lund University, Sweden;Department of Laboratory Medicine, Division of Pathology, Lund University Hospital, Sweden;

关键词: Vascular Endothelial Growth Factor;    Androgen Receptor;    Benign Prostate Hyperplasia;    LNCaP Cell;    Prostate Tissue;   

DOI  :  10.1186/1471-2407-10-385

 received in 2010-01-18, accepted in 2010-07-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundNeuroendocrine (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 1α (HIF1α), in both benign and malignant NE prostate cells. HIF1α and HIF1β are two subunits of HIF1, a transcription factor important for angiogenesis. The aim of this study was to elucidate whether the cytoplasmic stabilization of HIF1α in androgen independent NE differentiated prostate cancer is due to the presence of certain HIF1α isoforms.MethodsWe studied the HIF1α 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.ResultsWe identified multiple isoforms in both benign and malignant prostate tissues. One of these isoforms, HIF1α1.2, which was previously reported to be testis specific, was found in 86% of NE-differentiated prostate tumors, 92% of HIF1α 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 HIF1α present in androgen-independent NE cells of benign and malignant prostate tissue and co-localizes with immunoreactive cytoplasmic HIF1β.ConclusionOur results indicate that the cytoplasmic stabilization of HIF1α in NE-differentiated cells in benign and malignant prostate tissue is due to presence of an HIF1α isoform, HIF1α1.2. Co-localization of this isoform with HIF1β indicates that the HIF1α1.2 isoform might sequester HIF1β in the cytoplasm.

【 授权许可】

CC BY   
© Monsef et al; licensee BioMed Central Ltd. 2010