dc.contributor.author | Chakravarthy, Reka | |
dc.contributor.author | Mnich, Katarzyna | |
dc.contributor.author | Gorman, Adrienne M. | |
dc.date.accessioned | 2016-10-18T08:46:56Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Chakravarthy, Reka, Mnich, Katarzyna, & Gorman, Adrienne M. (2016). Nerve growth factor (NGF)-mediated regulation of p75NTR expression contributes to chemotherapeutic resistance in triple negative breast cancer cells. Biochemical and Biophysical Research Communications, 478(4), 1541-1547. doi: http://dx.doi.org/10.1016/j.bbrc.2016.08.149 | en_IE |
dc.identifier.issn | 1090-2104 | |
dc.identifier.uri | http://hdl.handle.net/10379/6070 | |
dc.description.abstract | Triple negative breast cancer [TNBC] cells are reported to secrete the neurotrophin nerve growth factor [NGF] and express its receptors, p75 neurotrophin receptor [p75(NTR)] and TrkA, leading to NGF-activated pro-survival autocrine signaling. This provides a rationale for NGF as a potential therapeutic target for TNBC. Here we show that exposure of TNBC cells to NGF leads to increased levels of p75(NTR), which was diminished by NGF-neutralizing antibody or NGF inhibitors [Ro 08-2750 and Y1086]. NGF-mediated increase in p75(NTR) levels were partly due to increased transcription and partly due to inhibition of proteolytic processing of p75(NTR). In contrast, proNGF caused a decrease in p75(NTR) levels. Functionally, NGF-induced increase in p75(NTR) caused a decrease in the sensitivity of TNBC cells to apoptosis induction. In contrast, knock-down of p75(NTR) using shRNA or small molecule inhibition of NGF-p75(NTR) interaction [using Ro 08-2750] sensitized TNBC cells to drug-induced apoptosis. In patient samples, the expression of NGF and NGFR [the p75(NTR) gene] mRNA are positively correlated in several subtypes of breast cancer, including basal-like breast cancer. Together these data suggest a positive feedback loop through which NGF-mediated upregulation of p75(NTR) can contribute to the chemo-resistance of TNBC cells. | en_IE |
dc.description.sponsorship | Higher Education Authority [PRTLI 5] and the Beckman Fund, School of Natural Sciences, NUI Galway, Ireland. K.M. is funded by an Irish Research Council Fellowship (GOIPD/2014/53). | en_IE |
dc.format | application/pdf | en_IE |
dc.language.iso | en | en_IE |
dc.publisher | Elsevier | en_IE |
dc.relation.ispartof | Biochemical And Biophysical Research Communications | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | Apoptosis | en_IE |
dc.subject | Breast cancer cells | en_IE |
dc.subject | Nerve growth factor (NGF) | en_IE |
dc.subject | p75 neurotrophin receptor (p75NTR) | en_IE |
dc.title | Nerve growth factor (NGF)-mediated regulation of p75(NTR) expression contributes to chemotherapeutic resistance in triple negative breast cancer cells | en_IE |
dc.type | Article | en_IE |
dc.date.updated | 2016-10-18T08:33:52Z | |
dc.identifier.doi | 10.1016/j.bbrc.2016.08.149 | |
dc.local.publishedsource | http://dx.doi.org/10.1016/j.bbrc.2016.08.149 | en_IE |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | |~| | |
dc.description.embargo | 2017-08-27 | |
dc.internal.rssid | 11545754 | |
dc.local.contact | Adrienne Gorman, Biochemistry, School Of Natural Science, Bioresearch Building, Nui. 2417 Email: adrienne.gorman@nuigalway.ie | |
dc.local.copyrightchecked | No | |
dc.local.version | ACCEPTED | |
nui.item.downloads | 579 | |