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Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Butterworth, Karl T, McCarthy, Helen O, Devlin, Andrea, Ming, Louise, Robson, Tracy, McKeown, Stephanie and Worthington, Jenny (2008) Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype. INTERNATIONAL JOURNAL OF CANCER, 123 (4). pp. 760-768. [Journal article]

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DOI: 10.1002/ijc.23418

Abstract

Hypoxia confers resistance to common cancer therapies, however, it has also has been shown to result in genetic alterations which may allow a survival advantage and increase the tumorigenic properties of cancer cells. Additionally, it may exert a selection pressure, allowing expansion of tumor cells with a more aggressive phenotype. To further assess the role of hypoxia in malignant progression in prostate cancer we exposed human androgen dependent prostate cancer cells (LNCaP) to cycles of chronic hypoxia and isolated a subline, LNCaP-H1. This article describes the partial characterization of this cell line. The LNCaP-H1 subline showed altered growth characteristics and exhibited androgen independent growth both in vitro and in vivo. Furthermore, these cells were resistant to mitochondrial-mediated apoptosis, probably since the endogenous levels of Bax was lower and Bcl-2 higher than in the parental LNCaP cells. Microarray analysis revealed that a complex array of pathways had differential gene expression between the 2 cell lines, with LNCaP-H1 cells exhibiting a genetic profile which suggests that they may be more likely metastasize to distant organs, especially bone. This was supported by an in vitro invasion assay, and an in vivo metastasis study. This study shows that hypoxia can select for androgen independent prostate cancer cells which have a survival advantage and are more likely to invade and metastasize. (c) 2008 Wiley-Liss. Inc.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Molecular Medicine
Biomedical Sciences Research Institute > Pharmaceutical Science and Practice
Biomedical Sciences Research Institute > Molecular Medicine > Transcriptional Regulation & Epigenetics
ID Code:4302
Deposited By:Professor Stephanie McKeown
Deposited On:21 Dec 2009 12:23
Last Modified:23 Jun 2011 15:54

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