LNCaP: ARW741L cell line
- Institute Northern Institute For Cancer Research, Newcastle University
Tool name: LNCaP: ARW741L cell line
Alternate names: AR, Dihydrotestosterone Receptor, Nuclear Receptor Subfamily 3 Group C Member 4, NR3C4, DHTR
Tool type: Cell Lines
Tool sub-type: Continuous
Parental cell line: LNCaP
Cancer type: Human prostate adenocarcinoma
Description: 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
Research area: Cancer
- For Research Use Only
- • 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.