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 McKeown, Jenny Worthington

    Research output: Contribution to journalArticle

    45 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. (c) 2008 Wiley-Liss. Inc.
    LanguageEnglish
    Pages760-768
    JournalInternational Journal of Cancer
    Volume123
    Issue number4
    DOIs
    Publication statusPublished - Aug 2008

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    Androgens
    Genotype
    Phenotype
    Prostatic Neoplasms
    Cell Line
    Neoplasms
    Survival
    Microarray Analysis
    Growth
    Hypoxia
    Apoptosis
    Neoplasm Metastasis
    Gene Expression
    Pressure
    Bone and Bones

    Cite this

    Butterworth, K. T., McCarthy, H. O., Devlin, A., Ming, L., Robson, T., McKeown, S., & Worthington, J. (2008). Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype. International Journal of Cancer, 123(4), 760-768. https://doi.org/10.1002/ijc.23418
    Butterworth, Karl T ; McCarthy, Helen O ; Devlin, Andrea ; Ming, Louise ; Robson, Tracy ; McKeown, Stephanie ; Worthington, Jenny. / Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype. In: International Journal of Cancer. 2008 ; Vol. 123, No. 4. pp. 760-768.
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    Butterworth, KT, McCarthy, HO, Devlin, A, Ming, L, Robson, T, McKeown, S & Worthington, J 2008, 'Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype', International Journal of Cancer, vol. 123, no. 4, pp. 760-768. https://doi.org/10.1002/ijc.23418

    Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype. / Butterworth, Karl T; McCarthy, Helen O; Devlin, Andrea; Ming, Louise; Robson, Tracy; McKeown, Stephanie; Worthington, Jenny.

    In: International Journal of Cancer, Vol. 123, No. 4, 08.2008, p. 760-768.

    Research output: Contribution to journalArticle

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