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  • Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells

    Author(s)
    Huang, Kuan-Chun
    Yang, Junzheng
    Ng, Michelle C
    Ng, Shu-Kay
    Welch, William R
    Muto, Michael G
    Berkowitz, Ross S
    Ng, Shu-Wing
    Griffith University Author(s)
    Ng, Shu Kay Angus
    Year published
    2016
    Metadata
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    Abstract
    Abstract Background: The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterisation of chemoresponse-associated biomarkers are of paramount importance for novel therapeutic development. Methods: Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harbouring cyclin A1-inducible expression construct were compared with and without tetracycline induction, as well as when the cyclin A1 expression was ...
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    Abstract Background: The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterisation of chemoresponse-associated biomarkers are of paramount importance for novel therapeutic development. Methods: Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harbouring cyclin A1-inducible expression construct were compared with and without tetracycline induction, as well as when the cyclin A1 expression was suppressed by short inhibiting RNA (siRNA). Cellular senescence was evaluated by b-galactosidase activity staining. Results: Global RNA expression profiling and subsequent correlation studies of gene expression level and drug response has identified that elevated expression of cyclin A1 (CCNA1) was significantly associated with cellular resistance to paclitaxel, doxorubicin and 5-fluorouracil. The role of cyclin A1 in paclitaxel resistance was confirmed in ovarian cancer cells that harbour an inducible cyclin A1 expression construct, which showed reduced paclitaxelmediated growth inhibition and apoptosis when cyclin A1 expression was induced, whereas downregulation of cyclin A1 expression in the same cell lines using cyclin A1-specific siRNAs sensitised the cells to paclitaxel toxicity. However, ovarian cancer cells with ectopic expression of cyclin A1 demonstrated slowdown of proliferation and senescence-associated b-galactosidase activity. Conclusions: Our profiling and correlation studies have identified cyclin A1 as one chemoresistance-associated biomarker in ovarian cancer. The results of the characterisation studies suggest that cyclin A1 functions as an oncogene that controls proliferative and survival activities in tumourigenesis and chemoresistance of ovarian cancer.
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    Journal Title
    European Journal of Cancer
    Volume
    67
    DOI
    https://doi.org/10.1016/j.ejca.2016.08.007
    Subject
    Oncology and carcinogenesis
    Oncology and carcinogenesis not elsewhere classified
    Health services and systems
    Public health
    Publication URI
    http://hdl.handle.net/10072/100459
    Collection
    • Journal articles

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