In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 8 ( 2012-02-21), p. 2730-2735
Abstract:
Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen. This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1 , CLPP , GPRC5D , NAE1 , NF1 , NIPBL , NSD1 , RAD21 , RARG , SMC3 , and UBA3 ) and also a set of genes whose silencing causes sensitivity to this endocrine agent ( C10orf72 , C15orf55/NUT , EDF1 , ING5 , KRAS , NOC3L , PPP1R15B , RRAS2 , TMPRSS2 , and TPM4 ). Multiple individual genes, including NF1 , a regulator of RAS signaling, also correlate with clinical outcome after tamoxifen treatment.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1018872108
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2012
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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