Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
2013 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 4, 2175- p.Article in journal (Refereed) Published
About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
Place, publisher, year, edition, pages
2013. Vol. 4, 2175- p.
IdentifiersURN: urn:nbn:se:su:diva-94193DOI: 10.1038/ncomms3175ISI: 000323716600011OAI: oai:DiVA.org:su-94193DiVA: diva2:652465
Swedish Research Council; GlycoHit FP7 EU project; Swedish Cancer Society; Stockholm's cancer Society; Swedish State under the LUA-agreement (Sahlgrenska University Hospital, Gothenburg) VGFOUREG-75911; King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg 2009: 49; Linköping University Hospital Research Foundation, Linköping; Gosta Miltons Donationsfond, Stockholm, Sweden 802004 2013-09-302013-09-302016-04-25