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

Karl T. Butterworth, Helen O. McCarthy, Andrea Devlin, Louise Ming, Tracy Robson, Stephanie R. McKeown, Jenny Worthington

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)760-768
Number of pages9
JournalInternational Journal of Cancer
Volume123
Issue number4
Early online date29 May 2008
DOIs
Publication statusPublished - 15 Aug 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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