Abstract
Author SummaryThe molecular subtypes of breast cancer are distinguished by their intrinsic patterns of gene expression and can be used to group patients with different prognoses and treatment options. Although molecular subtyping tests are currently under evaluation, some of them are already in use to better tailor therapy for patients; however, the molecular events that are responsible for these different patterns of gene expression in breast cancer are largely undefined. The elucidation of their mechanistic basis would improve our understanding of the disease process and enhance the chances of developing better predictive and prognostic markers, new therapies, and interventions to overcome resistance to existing therapies. Here, we show that the transcription factor ELF5 is responsible for much of the patterning of gene expression that distinguishes the breast cancer subtypes. Additionally, our data suggest that ELF5 may also be involved in the development of resistance to therapies designed to stop estrogen stimulation of breast cancer. These effects of ELF5 appear to represent a partial carryover into breast cancer of its normal role in the mammary gland, where it is responsible for the development of milk-producing structures during pregnancy.
Highlights
The molecular subtypes of breast cancer are distinguished by their intrinsic patterns of gene expression [1] that have been refined to become prognostic tests under evaluation or in use [2]
In this report we show that ELF5 exerts wide transcriptional effects with functional outcomes on cell proliferation, adhesion, the molecular determinants of breast cancer subtype and phenotype, and acquired resistance to Tamoxifen
Recent findings show that estrogen receptor (ER)-chromatin binding and the resulting transcriptional response to estrogens are dependent on FOXA1 expression and its action as a pioneer factor for chromatin-ER binding [3]
Summary
The molecular subtypes of breast cancer are distinguished by their intrinsic patterns of gene expression [1] that have been refined to become prognostic tests under evaluation or in use [2]. Molecular subtyping tests are currently under evaluation, some of them are already in use to better tailor therapy for patients; the molecular events that are responsible for these different patterns of gene expression in breast cancer are largely undefined. The elucidation of their mechanistic basis would improve our understanding of the disease process and enhance the chances of developing better predictive and prognostic markers, new therapies, and interventions to overcome resistance to existing therapies. Our data suggest that ELF5 may be involved in the development of resistance to therapies designed to stop estrogen stimulation of breast cancer. These effects of ELF5 appear to represent a partial carryover into breast cancer of its normal role in the mammary gland, where it is responsible for the development of milk-producing structures during pregnancy
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