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Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like breast cancer and engineering of interference peptides block its oncogenic function by A S Beltran; L M Graves; P Blancafort is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Novel role of Engrailed 1 as a prosurvival transcription factor in basal-like breast cancer and engineering of interference peptides block its oncogenic function about?

Basal-like breast tumors are aggressive cancers associated with high proliferation and metastasis. Chemotherapy is currently the only treatment option; however, resistance often occurs resulting in recurrence and patient death. Some extremely aggressive cancers are also associated with hypoxia, inflammation and high leukocyte infiltration. Herein, we discovered that the neural-specific transcription factor, Engrailed 1 (EN1), is exclusively overexpressed in these tumors. Short hairpin RNA (shRNA)-mediated knockdown of __EN1__ triggered potent and selective cell death. In contrast, ectopic overexpression of __EN1__ in normal cells activated survival pathways and conferred resistance to chemotherapeutic agents. Exogenous expression of __EN1__ cDNA reprogrammed the breast epithelial cells toward a long-lived, neural-like phenotype displaying dopaminergic markers. Gene expression microarrays demonstrated that the __EN1__ cDNA altered transcription of a high number of inflammatory molecules, notably chemokines and chemokine receptors, which could mediate prosurvival pathways. To block EN1 function, we engineered synthetic interference peptides (iPeps) comprising the EN1-specific sequenc

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Author

A S Beltran; L M Graves; P Blancafort

Publisher

Springer Science and Business Media LLC

Published

2013

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)