Mutation screening of the androgen receptor promoter and untranslated regions in prostate cancer.
BACKGROUND
Mechanisms, other than gene amplification, leading to overexpression of AR in androgen ablation-resistant prostate cancer remain unknown and could include genetic alterations in the promoter or untranslated regions (UTR) of the AR gene.


METHODS
DNAs from five prostate cancer cell lines, 19 LuCaP xenografts, 44 clinical tumors, and 36 non-malignant controls were used for screening mutations in the upstream regulatory region, promoter and the 5'- and 3'-UTRs of the AR gene with denaturating high performance liquid chromatography (DHPLC) and sequencing.


RESULTS
Ten different sequence variations were found in prostate cancer cell lines and xenografts. However, none of them were recurrent or were found in clinical prostate cancer specimens or in normal controls.


CONCLUSIONS
Recurrent mutations in the promoter or UTRs of AR seem to be rare, and thus not likely mechanisms for the increased expression of the gene in the androgen ablation-resistant prostate cancer.
Waltering
Kati K
KK
Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Wallén
Mika J
MJ
Tammela
Teuvo L J
TL
Vessella
Robert L
RL
Visakorpi
Tapio
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020506:Untranslated Regions
D017931:DNA Primers; D004273:DNA, Neoplasm; D011944:Receptors, Androgen; D020506:Untranslated Regions