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Catalogue Number 154165
Antigen/Gene or Protein Targets Androgen Receptor
Parental Line LNCaP
Synonyms AR, Dihydrotestosterone Receptor, Nuclear Receptor Subfamily 3 Group C Member 4, NR3C4, DHTR
Host Human
Disease Keywords Human prostate adenocarcinoma
Model Tumour line
Relevance LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old Caucasian male in 1977. The androgen receptor (AR) in LNCaP cells harbours a T877A mutations which enables the anti-androgen flutamide to act as an agonist. This cell line is the most commonly used for prostate cancer research.
In approximately 30% CRPC, AR mutations are detected and are likely selected for under pressure by hormonal therapies.Mutations within the AR ligand-binding domain, the site of testosterone and anti-androgen binding, enable retention of AR signalling in the presence of hormonal therapies. Two AR LBD mutations are commonly detected in patients treated with bicalutamide and enzalutamide, W741L and F876L,
respectively. These convert the activity of anti-androgens from antagonists to agonists and enable progression of CRPC. Modelling these mutations previously has been difficult and have been limited to, principally, luciferase-based assays in non-AR-expressing cell lines.
We have therefore developed two key LNCaP cell derivatives that have stable expression of ARW741L and ARF876L (Cat No:154163) mutations which enables us to assess the activity of these aberrantly functioning receptors in a physiological background. Moreover, by depleting endogenous AR in LNCaP cells, we can provide a ‘clean’ read-out for mutant AR activity that can be utilised for assessing efficacy of novel AR-targeting agents
Production Details HEK 293T cells were transfected with pLenti-FLAG-ARF876L to generate viral particles. Using a multiplicity of infection of 0.3 and 0.1, LNCaP cells were transduced with virus. Stable expressing clones were selected with 10µg/ml blasticidin. Ectopic AR expression was determined by western blot
Conditional No
Research Area Cancer
Recommended Growing Conditions RPMI-1640 + 10% FBS

References

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References: 2 entries

O'Neill et al. 2015. Oncotarget. 6(28):26029-40. PMID: 26267320.

Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

Europe PMC ID: 26267320


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References: 2 entries

O'Neill et al. 2015. Oncotarget. 6(28):26029-40. PMID: 26267320.

Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.


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