Genomics

Dataset Information

304

SRC-1 targets ADAM22: an ER-independent mechanism of tumour progression in endocrine resistance


ABSTRACT: We profile the binding of Steroid Receptor Co-activator (SRC1) in LY2 cells, a tamoxifen-resistant cell line, in the presence and absence of tamoxifen using ChIP-sequencing technology. The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity leading to the development of a steroid-independent tumour. The p160 steroid coactivataor protein SRC-1, through interactions with developmental proteins and other non-steroidal transcription factors, drives this tumour adaptability. Here, using discovery studies, we identify ADAM22, a non-protease member of the ADAMs family, as a direct, ER-independent target of SRC-1. Molecular, cellular and in vivo studies confirmed SRC-1 as a regulator of ADAM22. At a functional level, a role for ADAM22 in cellular migration and differentiation was observed. In vivo data from a mouse xenograft model indicated that ADAM22 expression was higher in 4-OHT-treated endocrine-resistant tumours than in tumours derived from isogenic, sensitive cells. Furthermore, in breast cancer patients, ADAM22 expression is an independent predictor of poor disease free survival. SRC-1 can function as a molecular switch which converts a steroid-responsive tumour to a steroid-resistant tumour. The ER-independent SRC-1 target ADAM22 is a potential drug target and a companion predictive biomarker in the treatment of endocrine-resistant breast cancer. Examination of SRC-1 binding in LY2 cells in the presence or absence of tamoxifen treatment. 2 replicates each.

ORGANISM(S): Homo sapiens  

SUBMITTER: Ailis Fagan  

PROVIDER: E-GEOD-28987 | ArrayExpress | 2011-11-01

SECONDARY ACCESSION(S): SRP008016GSE28987PRJNA140501

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer.

McCartan Damian D   Bolger Jarlath C JC   Fagan Aílis A   Byrne Christopher C   Hao Yuan Y   Qin Li L   McIlroy Marie M   Xu Jianming J   Hill Arnold D AD   Gaora Peadar Ó PÓ   Young Leonie S LS  

Cancer research 20111109 1


The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence of a hormone-independent tumor. The steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In this discovery study, we identified ADAM22, a non-protease member of the ADAM family of disintegrins, as a direct estrogen receptor (ER)-independent target of  ...[more]

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