Glucocorticoid receptor over-expression promotes human small cell lung cancer apoptosis in vivo and thereby slows tumor growth

Paula Sommer, Rachel L. Cowen, Andrew Berry, Ann Cookson, Brian A. Telfer, Kaye J. Williams, Ian J. Stratford, Paul Kay, Anne White, David W. Ray

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Small cell lung cancer (SCLC) is an aggressive tumor, associated with ectopic ACTH syndrome. We have shown that SCLC cells are glucocorticoid receptor (GR) deficient, and that restoration of GR expression confers glucocorticoid sensitivity and induces apoptosis in vitro. To determine the effects of GR expression in vivo, we characterized a mouse SCLC xenograft model that secretes ACTH precursor peptides, and so drives high circulating corticosterone concentrations (analogous to the ectopic ACTH syndrome). Infection of SCLC xenografts with GR-expressing adenovirus significantly slowed tumor growth compared with control virus infection. Time to fourfold initial tumor volume increased from a median of 9 days to 16 days (P=0.05; n=7 per group). Post-mortem analysis of GR-expressing tumors revealed a threefold increase in apoptotic (TUNEL positive) cells (P
    Original languageEnglish
    Pages (from-to)203-213
    Number of pages10
    JournalEndocrine-related cancer
    Volume17
    Issue number1
    DOIs
    Publication statusPublished - Mar 2010

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