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HOXB7 is an ERÎ± cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance

ABSTRACT: Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor alpha (ERÎ±) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 ChIP analysis followed by validation showed that HOXB7 physically interacts with ERÎ±, and that the HOXB7-ERÎ± complex enhances transcription of many ERÎ± target genes including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR-HER2 signaling, inhibits transcription of miRNA-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER-target genes and HER2. Repressing MYC using small molecule inhibitors reverses these events, and causes regression of breast cancer xenografts. The MYC-HOXB7-HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer. MCF7 cell lines stably transduced with either vector control of HOXB7. Array ran in duplicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Saraswati Sukumar

PROVIDER: E-GEOD-63607 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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HOXB7 is an ERα cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance

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