Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer.
This study examined androgen receptor (AR) gene amplification and protein expression in 102 matched paired hormone sensitive and resistant tumours from 51 patients. AR gene amplification and X chromosome copy number were assessed by fluorescent in situ hybridisation, and protein expression was assessed by immunohistochemistry. All tumours were stained for PSA protein expression. Significantly more tumours exhibited AR amplification following the development of hormone resistance (20%, 10 out of 49) compared to matched hormone-sensitive tumours from the same patient (2%, one out of 48) (P=0.0085). The level of AR expression was significantly higher in hormone-resistant tumours compared to matched hormone-sensitive tumours from the same patient (130, interquartile range, 55-167 vs 94.5 interquartile range, 55-120, P=0.019). AR expression levels in hormone-resistant tumours with and without AR amplification were not significantly different. However, an increase in AR expression was seen with the development of AR amplification in paired tumours. The rate of AR gene amplification and/or an increase in AR protein expression during androgen resistant is too low to wholly explain the development of androgen resistance. Alternative mechanisms for modulating the function of the AR, or other signalling pathways, must be considered as key factors in the development of hormone-resistant prostate.
Edwards
J
J
Endocrine Cancer Group, Surgical and Translational research section, Division of Cancer Sciences and Molecular Pathology, Glasgow Royal Infirmary, Glasgow G31 2ER, Scotland.
Krishna
N S
NS
Grigor
K M
KM
Bartlett
J M S
JM
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D041321:Chromosomes, Human, X / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction
D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen