Regulation of gene expression by the androgen receptor and hedgehog pathways in breast cancer cells

Vivian Yar Li Chua

    Research output: ThesisDoctoral Thesis

    483 Downloads (Pure)

    Abstract

    [Truncated] The androgen receptor (AR) is expressed in 70-90% of breast tumours and its increased

    expression in oestrogen receptor (ER) expressing breast cancers is correlated with better disease
    prognosis and longer relapse-free and overall survival. The Hedgehog signalling pathway has also
    been implicated in breast cancer growth, with Hedgehog signalling intermediates and
    Hedgehog-induced target genes overexpressed in both early stage and aggressive breast tumours. The
    androgen, 5α-dihydrotestosterone (DHT) and the Hedgehog pathway inhibitor, cyclopamine, inhibit
    proliferation of the MCF-7 and T- 47D breast cancer cell lines and this thesis has investigated
    genes and cellular processes regulated by these agents that would potentially impede breast tumour
    progression. In DHT and cyclopamine treated MCF-7 and T-47D cells, screening of gene expression
    using RT2 Profiler Human Breast Cancer PCR Arrays identified decreased expression of

    both the ABC transporters, ABCB1 and ABCG2, which facilitate the development of drug resistance in
    cancer cells, and regulators of epithelial-to-mesenchymal transition (EMT), a program associated
    with induction of cancer cell motility, invasiveness and metastasis.









    Original languageEnglish
    QualificationDoctor of Philosophy
    Supervisors/Advisors
    • Yeap, Bu, Supervisor
    • Harvey, Jennet, Supervisor
    • Bentel, Jacqueline, Supervisor
    Publication statusUnpublished - 2015

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