dc.contributor.author | Huang, Kuan-Chun | |
dc.contributor.author | Yang, Junzheng | |
dc.contributor.author | Ng, Michelle C | |
dc.contributor.author | Ng, Shu-Kay | |
dc.contributor.author | Welch, William R | |
dc.contributor.author | Muto, Michael G | |
dc.contributor.author | Berkowitz, Ross S | |
dc.contributor.author | Ng, Shu-Wing | |
dc.date.accessioned | 2018-02-20T00:56:50Z | |
dc.date.available | 2018-02-20T00:56:50Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.doi | 10.1016/j.ejca.2016.08.007 | |
dc.identifier.uri | http://hdl.handle.net/10072/100459 | |
dc.description.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 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. | |
dc.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 152 | |
dc.relation.ispartofpageto | 163 | |
dc.relation.ispartofjournal | European Journal of Cancer | |
dc.relation.ispartofvolume | 67 | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Oncology and carcinogenesis not elsewhere classified | |
dc.subject.fieldofresearch | Health services and systems | |
dc.subject.fieldofresearch | Public health | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 321199 | |
dc.subject.fieldofresearchcode | 4203 | |
dc.subject.fieldofresearchcode | 4206 | |
dc.title | Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Ng, Shu Kay Angus | |