Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

Narayanan, Ramesh; Dalton, James T.

doi:10.3390/cancers8120108

Cited by 58 publications

(47 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent review summarized conflicting data of preclinical researches on the complex role of AR in TNBC [29]. In our study, we detected that AR was highly expressed in about 35.8% of TNBC patients.…”

Section: Discussionmentioning

confidence: 49%

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Shen

Yang

Zhang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The targeted therapy for triple-negative breast cancer (TNBC) is still challenging due to poor understanding on its molecular etiology. The androgen receptor (AR) has recently emerged as a prognostic and treatment-predictive marker in breast cancer. However, the role of AR in TNBC remained elusive. Methods: Immunohistochemistry (IHC) was used to detect AR and G-protein coupled estrogen receptor (GPER) expression in tissue microarrays of 165 TNBC patients. Microarray analysis of mRNAs was performed to identify downstream regulators of AR. TNBC cells were cultured with dihydrotestosterone (DHT) alone or in combination with AR knockdown performed with AR shRNA. Cell viability and colony formation were assessed. Western blotting and qRT-PCR were used to examine protein and mRNA expression, respectively. The potential mechanism of AR-mediated GPER suppression was identified by Chromatin immunoprecipitation (ChIP) assay. AR and GPER expressions were also assessed in nude mouse xenografts by IHC. Results: IHC staining showed that the expression of AR was positively associated with tumor size, lymph node metastasis and high-grade tumor in TNBC patients. AR activation triggered by DHT suppressed GPER expression, to promote cell growth of TNBC. G-1, a GPER agonist, inhibited DHT-stimulated proliferation. Further experiments illustrated that AR suppressed GPER activation via binding directly to the promoter of GPER. Moreover, a negative correlation between AR and GPER was observed in MDA-MB-231 tumor cell xenografts and TNBC patient samples. Conclusions: The suppression of GPER via AR may be involved in the positive actions towards the TNBC progression, making it a promising therapeutic target for TNBC treatment.

show abstract

Section: Discussionmentioning

confidence: 49%

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Shen

Yang

Zhang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…This concept will be evaluated in future clinical trials. The reader is referred to a recent review for detailed information on the potential role of AR in breast cancer (103). …”

Section: Potential Clinical Uses Of Sarmsmentioning

confidence: 99%

Development of selective androgen receptor modulators (SARMs)

Narayanan

Coss

Dalton

2018

Molecular and Cellular Endocrinology

Self Cite

193

139

View full text Add to dashboard Cite

The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits.

show abstract

“…Given that AR expression is a defining feature of carcinoma with apocrine differentiation, it is feasible that AR may, at least in part, contribute to poor prognosis in this subtype [23]. This concept is supported by in vitro studies demonstrate that AR signalling promotes proliferation of cell models in carcinoma with apocrine differentiation and is inhibited by AR antagonist or AR silencing [24]. The androgen signalling associated with these tumours may lead to the development with of new therapeutic modalities for these tumours in the future.…”

Section: Discussionmentioning

confidence: 95%

Expression features of androgen receptor in special subtypes of breast cancer

Xiang

Liu

Cao

et al. 2019

Preprint

View full text Add to dashboard Cite

Purpose The important role of the androgen receptor (AR) in invasive carcinoma of no specific type (NST) has been increasingly recognised. However, only a few studies have been reported in special subtypes of breast cancer. Thus, we aim to investigate the AR expression and its expression features in special subtypes of breast cancer. Methods This study collected clinicopathological data of 718 special subtypes of breast cancer from Tianjin Medical University Cancer Institute and Hospital. Immunohistochemical staining of AR and other biomarkers was performed. Results If the threshold of AR is ≥ 1%, the positive rate of AR in specific subtypes of breast cancer is 77.9% (559/718) of cases. Compared with the threshold of AR is ≥ 10%, the positive percentage of AR in each subtype of breast cancer increases about 10%. The positive expression rate of AR in carcinomas with apocrine differentiation is highest, and the coloration intensity is much stronger than that of other subtypes. The positive expression rate of AR is lowest in metaplastic carcinomas, almost negative; the positive expression rate of AR in invasive lobular carcinomas (ILCs), invasive micropapillary carcinomas (IMPCs), invasive papillary carcinomas (IPCs), and is mucinous carcinomas about 70.0%–80.0%. Conclusions The expression features of AR in special subtypes of breast cancer vary in different subtypes, and to some extent, AR may be a useful biomarker for clinical diagnosis. Routine testing of AR has a certain guiding significance for clinical work. In addition, AR is expected to treat carcinomas with apocrine differentiation as a target.

show abstract

Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

Cited by 58 publications

References 108 publications

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer

Development of selective androgen receptor modulators (SARMs)

Expression features of androgen receptor in special subtypes of breast cancer

Contact Info

Product

Resources

About