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Updated: Mar 30, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Expression of androgen receptor splice variants in clinical breast cancers
Theresa E Hickey1, Connie M Irvine1, Heidi Dvinge2,3
1Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, The University of Adelaide, SA 5005, Australia.
Abstract:
The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERα-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERα-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer.
Insights
Androgen receptor variants (AR-Vs), like AR-V7, are common in breast cancer and can drive tumor growth independently of androgen signaling. These variants may predict resistance to androgen deprivation therapy (ADT) in clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) signaling is crucial in breast cancer, leading to clinical trials for androgen deprivation therapy (ADT).
- Resistance to ADT in prostate cancer is linked to constitutively active AR splice variants (AR-Vs).
- Similar AR variants may occur in breast cancer, impacting treatment efficacy.
Purpose of the Study:
- To investigate the presence and function of AR variants in primary breast tumors.
- To determine the expression levels and clinical relevance of AR-V7 in breast cancer.
- To assess the impact of AR-V7 on treatment response to ADT.
Main Methods:
- Analysis of AR variant transcripts in primary breast tumors using molecular techniques.
- Detection of AR-V7 at both mRNA and protein levels.
- Functional studies of AR-V7 in ERα-negative breast cancer cells.
- Ex vivo experiments assessing AR-V7 upregulation by enzalutamide.
Main Results:
- Diverse AR-V transcripts are produced by the AR gene in breast tumors.
- AR-V7 (exons 1/2/3/CE3) is the most frequent and highly expressed variant, found in over 50% of breast cancers at the mRNA level.
- AR-V7 protein is detected in a subset of ERα-negative tumors.
- AR-V7 is a constitutively active, ADT-resistant transcription factor promoting distinct transcriptional programs in ERα-negative cells.
- Ex vivo studies show enzalutamide upregulates AR-V7 in primary breast tumors.
Conclusions:
- AR-V7 is a prevalent and functionally significant AR splice variant in breast cancer.
- AR-V7 expression may indicate resistance to ADT and influence treatment outcomes.
- Findings have implications for ongoing and future ADT clinical trials in breast cancer.
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