UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

POU4F2/Brn-3b transcription factor is associated with survival and drug resistance in human ovarian cancer cells

Maskell, LJ; Mahadeo, AV; Budhram-Mahadeo, VS; (2018) POU4F2/Brn-3b transcription factor is associated with survival and drug resistance in human ovarian cancer cells. Oncotarget , 9 (95) pp. 36770-36779. 10.18632/oncotarget.26371. Green open access

[thumbnail of 26371-1016087-7-PB.pdf]
Preview
Text
26371-1016087-7-PB.pdf - Published Version

Download (3MB) | Preview

Abstract

The development of drug resistance following treatment with chemotherapeutic agents such as cisplatin (cis) and paclitaxel (pax) contributes to high morbidity and mortality in ovarian cancers. However, the molecular mechanisms underlying such changes are not well understood. In this study, we demonstrate that the Brn-3b transcription factor was increased in different ovarian cancer cells including SKOV3 and A2780 following treatment with cis and pax. Furthermore, sustained increases in Brn-3b were associated with survival in drug resistant cells and correlated with elevated HSP27 expression. In contrast, targeting Brn-3b for reduction using short interfering RNA (siRNA) also resulted in attenuated HSP27 expression. Importantly, blocking Brn-3b expression with siRNA in SKOV3 cells was associated with reduced cell numbers at baseline but also increased cell death after further treatment, indicating sensitization of cells. Similar results were obtained in the metastatic IP1 cell line derived from ascites of mice bearing SKOV3 tumours. These findings suggest that increased Brn-3b may confer resistance to chemotherapeutic drugs in ovarian cancer cells by regulating key target genes such as HSP27 and that targeting Brn-3b may provide a novel mechanism for treatment of drug resistant ovarian cancers.

Type: Article
Title: POU4F2/Brn-3b transcription factor is associated with survival and drug resistance in human ovarian cancer cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.26371
Publisher version: https://doi.org/10.18632/oncotarget.26371
Language: English
Additional information: Copyright @ Maskell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10065136
Downloads since deposit
75Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item