Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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SRC1 gene regulation in endocrine resistant breast cancer cells

ABSTRACT: 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 coactivator 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 target of SRC-1, independent of estrogen receptor(ER). Molecular, cellular, in vivo and clinical studies confirmed SRC-1 as a regulator of ADAM22 and established a role for ADAM22 in endocrine resistant tumour progression. ADAM22 has the potential to act as a therapeutic drug target and a companion predictive biomarker in the treatment of endocrine resistant breast cancer. 14 samples representing 4 conditions were analysed. Samples were transfected with either a siRNA targetting SRC1 or a control scrambled siRNA. Samples were subject to tamoxifen treatment or untreated.

ORGANISM(S): Homo sapiens

SUBMITTER: Yuan Hao 

PROVIDER: E-GEOD-28645 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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