Overexpression and gene amplification of BAG-1L in hormone-refractory prostate cancer.
BAG-1L (Bcl-2-associated anthanogene 1) has been found to interact with androgen receptor (AR), and has been suggested to be involved in the development of prostate cancer. In order to determine the presence of genetic and/or expression alterations of BAG-1L in prostate cancer, we analysed human prostate cancer cell lines and xenografts as well as patient samples of untreated, hormone-naïve, and hormone-refractory prostate carcinomas for sequence variations using denaturing high-performance liquid chromatography (DHPLC), for gene copy number using fluorescence in situ hybridization (FISH), and for expression using both quantitative RT-PCR and immunostaining. Only one sequence variation was found in all 37 cell lines and xenografts analysed. BAG-1 gene amplification was detected in two xenografts. In addition, gene amplification was found in 6 of 81 (7.4%) hormone-refractory clinical tumours, whereas no amplification was found in any of the 130 untreated tumours analysed. Additionally, gain of the BAG-1 gene was observed in 27.2% of the hormone-refractory tumours and in 18.5% of the untreated carcinomas. In a set of 263 patient samples, BAG-1L protein expression was significantly higher in hormone-refractory tumours than in primary tumours (p = 0.002). Altogether, these data suggest that amplification and overexpression of BAG-1L may be involved in the progression of prostate cancer.
Mäki
H E
HE
Cancer Genetics, Institute of Medical Technology, University of Tampere, and Tampere University Hospital, FIN-33104 University of Tampere, Tampere, Finland.
Saramäki
O R
OR
Shatkina
L
L
Martikainen
P M
PM
Tammela
T L J
TL
van Weerden
W M
WM
Vessella
R L
RL
Cato
A C B
AC
Visakorpi
T
T
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D017211:Treatment Failure
D018931:Antineoplastic Agents, Hormonal; C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011944:Receptors, Androgen; D014157:Transcription Factors