Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.

Hdl Handle:
http://hdl.handle.net/10034/605167
Title:
Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.
Authors:
Pickard, Mark R.; Williams, Gwyn T.
Abstract:
The putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.
Affiliation:
Keele University, United Kingdom
Citation:
Pickard, M. R., & Williams, G. T. (2014). Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Research and Treatment, 145(2). 359-370. http://dx/doi.org/10.1007/s10549-014-2974-y
Journal:
Breast Cancer Research and Treatment
Publication Date:
1-May-2014
URI:
http://hdl.handle.net/10034/605167
DOI:
10.1007/s10549-014-2974-y
Additional Links:
http://link.springer.com/article/10.1007%2Fs10549-014-2974-y
Type:
Article
Language:
en
Description:
The final publication is available at Springer via http://dx.doi.org/10.1007/s10549-014-2974-y
ISSN:
0167-6806
EISSN:
1573-7217
Sponsors:
Breast Cancer Campaign UK
Appears in Collections:
Institute of Medicine

Full metadata record

DC FieldValue Language
dc.contributor.authorPickard, Mark R.en
dc.contributor.authorWilliams, Gwyn T.en
dc.date.accessioned2016-04-13T12:02:52Zen
dc.date.available2016-04-13T12:02:52Zen
dc.date.issued2014-05-01en
dc.identifier.citationPickard, M. R., & Williams, G. T. (2014). Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Research and Treatment, 145(2). 359-370. http://dx/doi.org/10.1007/s10549-014-2974-yen
dc.identifier.issn0167-6806en
dc.identifier.doi10.1007/s10549-014-2974-yen
dc.identifier.urihttp://hdl.handle.net/10034/605167en
dc.descriptionThe final publication is available at Springer via http://dx.doi.org/10.1007/s10549-014-2974-yen
dc.description.abstractThe putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.en
dc.description.sponsorshipBreast Cancer Campaign UKen
dc.language.isoenen
dc.relation.urlhttp://link.springer.com/article/10.1007%2Fs10549-014-2974-yen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectGAS5en
dc.subjectncRNAen
dc.subjectapoptosisen
dc.subjectbreasten
dc.subjectcanceren
dc.subjectchemotherapyen
dc.titleRegulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.en
dc.typeArticleen
dc.identifier.eissn1573-7217en
dc.contributor.departmentKeele University, United Kingdomen
dc.identifier.journalBreast Cancer Research and Treatmenten
dc.date.accepted2000-01-01en
dc.date.accepted2014-04-17en
or.grant.openaccessNoen
rioxxterms.funderxxen
rioxxterms.identifier.projectxxen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2214-06-30en
This item is licensed under a Creative Commons License
Creative Commons
All Items in ChesterRep are protected by copyright, with all rights reserved, unless otherwise indicated.