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Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes: potential therapeutic ramifications
- Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research, vol 20, iss 24
- Publication Year :
- 2014
-
Abstract
- Purpose: To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC). Experimental Design: Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. In vitro and in vivo animal studies were also performed. Results: AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent AR splice variants, mutations, and extra AR gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no AR gene amplification was observed. In vitro knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and in vivo androgen-independent tumor growth. Conclusions: Our study provides new detailed information on the molecular and structural alterations associated with AR gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials. Clin Cancer Res; 20(24); 6570–81. ©2014 AACR.
- Subjects :
- Male
Cancer Research
Gene Dosage
Gene Expression
Salivary duct carcinoma
Androgen
Prostate cancer
Mice
Gene duplication
Ductal
Receptors
80 and over
2.1 Biological and endogenous factors
Salivary Ducts
Aetiology
Neoplasm Metastasis
Cancer
Regulation of gene expression
Aged, 80 and over
Gene knockdown
Tumor
Prostate Cancer
Middle Aged
Salivary Gland Neoplasms
Tumor Burden
Carcinoma, Ductal
Protein Transport
Oncology
Receptors, Androgen
Heterografts
Female
Biotechnology
Urologic Diseases
Adult
Transcriptional Activation
medicine.medical_specialty
Oncology and Carcinogenesis
Biology
Gene dosage
Article
Cell Line
Internal medicine
Cell Line, Tumor
medicine
Genetics
Animals
Humans
Oncology & Carcinogenesis
Aged
Neoplasm Staging
Animal
Carcinoma
medicine.disease
Androgen receptor
Alternative Splicing
Disease Models, Animal
Endocrinology
Disease Models
Mutation
Cancer research
Subjects
Details
- ISSN :
- 15573265
- Volume :
- 20
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Accession number :
- edsair.doi.dedup.....dff2d7039a3fa0507730ca46f9cfc841