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Androgen-regulated gene expression in prostate cancer
1Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Abstract:
Androgen-regulated gene expression is mediated by the ligand-activated androgen receptor. Androgen receptor target genes contain in the regulatory regions one or more androgen response elements. Development of the male urogenital tract, including the prostate, depends on an activated androgen receptor. Similarly, growth of the majority of prostate cancers is androgen-dependent. Therefore, endocrine therapy, aimed at inhibition of androgen receptor functioning, has been applied for many years. However, during therapy, apparently androgen receptor independent cancers continue to grow. In general, these tumors still express the androgen receptor, suggesting a functional role of the androgen receptor. In a proportion of late stage prostate tumors, mutations and amplification of the androgen receptor gene have been found. Additionally, it has been hypothesized that ligand-independent androgen receptor activation can be involved in hormone refractory prostate cancer.
Insights
Androgen receptor (AR) signaling drives prostate cancer growth. Despite endocrine therapy, some cancers persist, suggesting AR remains functional through mutations or ligand-independent activation in advanced prostate cancer.
Area of Science:
- Molecular Endocrinology
- Cancer Biology
- Prostate Cancer Research
Background:
- Androgen receptor (AR) signaling is crucial for male urogenital tract development and prostate cancer growth.
- Endocrine therapy targets AR to inhibit prostate cancer progression.
- AR-independent tumor growth occurs despite ongoing therapy, with AR still expressed.
Purpose of the Study:
- To investigate the role of the androgen receptor in hormone-refractory prostate cancer.
- To explore mechanisms of AR activation in late-stage prostate tumors.
Main Methods:
- Analysis of androgen receptor gene status in prostate tumors.
- Investigation of androgen receptor expression and potential activation pathways.
Main Results:
- Prostate cancers often remain androgen-dependent for growth.
- Late-stage prostate tumors can exhibit AR gene mutations or amplification.
- Ligand-independent AR activation is a potential mechanism in hormone-refractory prostate cancer.
Conclusions:
- The androgen receptor plays a significant role even in advanced, treatment-resistant prostate cancer.
- Understanding AR alterations and activation mechanisms is vital for improving prostate cancer therapy.