In vivo amplification of the androgen receptor gene and progression of human prostate cancer

@article{Visakorpi1995InVA,
  title={In vivo amplification of the androgen receptor gene and progression of human prostate cancer},
  author={Tapio Visakorpi and Eija-R. Hyytinen and Pasi A. Koivisto and Minna M. Tanner and Riitta Keinänen and Christopher Palmberg and Aarno Palotie and Teuvo L.J. Tammela and Jorma Isola and Olli Kallioniemi},
  journal={Nature Genetics},
  year={1995},
  volume={9},
  pages={401-406}
}
Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11–q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high–level AR… 

Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer.

Failure of conventional androgen deprivation therapy in prostate cancer may be caused by a clonal expansion of tumor cells that are able to continue androgen-dependent growth despite of the low concentrations of serum androgens.

Androgen receptor gene amplification: a novel molecular mechanism for endocrine therapy resistance in human prostate cancer.

Discovery of AR amplification as a possible molecular mechanism of therapy resistance in prostate cancer should prove useful for development of more effective endocrine therapy regimens as well as diagnostic and predictive tests for therapy failure.

Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence.

The data indicate that AR gene mutations occur commonly in advanced prostate cancers prior to endocrine treatment of disease and may contribute to altered androgen responsiveness of the tumors.

Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer

It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.

[Role of androgen receptors in hormone-refractory prostate cancer: molecular basics and experimental therapy approaches].

The first in vivo studies showed that the AR is still expressed or is even overexpressed in hormone-refractory PCA, and these findings should lead to the development of new therapeutic strategies.

Analysis of genetic changes underlying local recurrence of prostate carcinoma during androgen deprivation therapy.

The findings suggest that hormone-refractory prostate cancers are genetically very complex and show intratumor genetic heterogeneity.

Androgen receptor involvement in the progression of prostate cancer.

Genetic diagnosis and/or molecular-targeted therapy via AR pathways can be developed for hormone-refractory states and several co-factors between ARs and the transcriptional complex have been cloned and reports indicate that steroid receptor co-activator 1 is correlated with the hormone- Refractory progression of prostate cancer.

The androgen receptor: genetic considerations in the development and treatment of prostate cancer

Clinically, these mutations are important because they may lead to the growth of androgen-independent tumors and progression to a refractory state, and further characterization of AR mutations will lead to a more thorough understanding of their role in the development of prostate carcinomas.

Molecular analysis of the androgen receptor in ten prostate cancer specimens obtained before and after androgen ablation.

It is concluded that in specific circumstances, AA treatments can select variant forms of the AR in the prostate of patients affected by prostate cancer.

Amplification and protein expression of androgen receptor gene in prostate cancer cells: Fluorescence in situ hybridization analysis.

An influential role of AR in tumor growth and progression even after the deprivation of androgen is demonstrated, as well as showing the potential contribution of AR amplification to AR activation even in the relative absence of androgens.
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