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Published on: December 9, 2015
A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression
Arvand Asghari1,2, Katherine Wall3,2, Michael Gill3
1Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
Abstract:
Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide. For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, an ER-positive tumor becomes unresponsive to endocrine therapy, and tumor regrowth occurs after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined. In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly change during cell modelling of endocrine resistant BC development. Expression of a subset of these genes was also differentially expressed in microarray analysis of endocrine-resistant and endocrine-sensitive tumor samples. Surprisingly, a subset of those genes was also differentially genes expressed in triple-negative breast cancer (TNBC) as compared with ER-positive BC. The findings suggest shared genetic mechanisms may underlie the development of endocrine resistant BC and TNBC. Our findings identify 34 novel genes for further study as potential therapeutic targets for treatment of endocrine-resistant BC and TNBC.
Insights
Researchers identified novel genes involved in endocrine therapy resistance in breast cancer (BC). These genes may also play a role in triple-negative breast cancer (TNBC), suggesting shared mechanisms for potential new treatments.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Breast cancer (BC) is a leading cause of cancer death in women globally.
- Endocrine therapy is effective for estrogen receptor-positive (ER-positive) BC, but resistance often develops.
- The genetic underpinnings of endocrine resistance in BC are not fully understood.
Purpose of the Study:
- To investigate dynamic gene expression changes during the development of endocrine resistance in BC.
- To identify novel genes associated with endocrine resistance and explore their potential role in triple-negative breast cancer (TNBC).
Main Methods:
- Utilized a novel statistical approach to analyze gene expression dynamics in cell models of endocrine-resistant BC.
- Performed microarray analysis comparing endocrine-resistant and endocrine-sensitive tumor samples.
- Compared gene expression profiles between endocrine-resistant BC and TNBC.
Main Results:
- Identified a novel group of genes with significantly altered time-course expression during endocrine resistance development.
- A subset of these genes showed differential expression in endocrine-resistant versus endocrine-sensitive tumors.
- Surprisingly, some identified genes were also differentially expressed in triple-negative breast cancer (TNBC) compared to ER-positive BC.
Conclusions:
- Shared genetic mechanisms may contribute to both endocrine-resistant BC and TNBC development.
- Identified 34 novel genes as potential therapeutic targets for endocrine-resistant BC and TNBC.
- Further research into these genes could lead to new treatment strategies for difficult-to-treat breast cancers.
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