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In half of ten men whose prostate cancer had stopped responding to hormone treatment, the receptor had changed shape so that other hormones, including oestrogen, could switch it on.
Complementary DNA was made from metastatic prostate cancers in 10 men with androgen-independent disease and the androgen receptor gene was amplified, cloned across exons B to H and sequenced. All the androgen-independent tumours expressed high levels of androgen receptor transcripts relative to the androgen-independent LNCaP cell line. Point mutations were identified in metastatic cells from 5 of the 10 men, one of them in the same codon as a mutation previously found in LNCaP. The mutations were not detectable in the primary tumours of two of those men. Functional studies of two of the mutant receptors in transfected cells showed that they could be activated by progesterone and by oestrogen.
It established that the receptor in resistant prostate cancer is not silent but promiscuous, which is why the specific allele matters clinically: a receptor that will accept a glucocorticoid or a progestogen changes what should and should not be prescribed alongside the hormonal agent.
Shares Androgen receptor signalling, Driver mutation, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares CYP17A1 (17-alpha-hydroxylase/17,20-lyase), Castration-resistant prostate cancer (CRPC), Androgen receptor, Metastatic castration-resistant prostate cancer.
Shares AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L), Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC).
Shares Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired), Androgen receptor.
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired), Androgen receptor.