Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer.
BACKGROUND
The mechanisms underlying the progression of prostate cancer to androgen-resistant cancer are still not fully understood. Here, we studied the genetic events associated with this transformation.


METHODS
The androgen sensitive prostate cancer cells line LNCaP-FGC and its androgen resistant subline LNCaP-r were investigated using SKY, CGH, and cDNA microarray.


RESULTS
Karyotypically, several additional chromosomal aberrations were seen in LNCaP-r as compared to the parental line. CGH also revealed unique net chromosomal alterations in LNCaP-r compared to LNCaP-FGC, including gain of 2p13-23, 2q21-32, and 13q and loss of 6p22-pter. cDNA microarray analysis identified several genes involved in DNA methylation, such as DNMT2, DNMT3a, and methyl-CpG binding domain protein 2 and 4 that were higher expressed in LNCaP-r. Interestingly, androgen responsiveness of LNCaP-r was restored after treated with DNA methyltransferase inhibitor.


CONCLUSIONS
Our findings may serve as a basis for molecular dissection of the mechanisms involved in development of androgen resistant prostate cancer.
Pang
See-Tong
ST
Department of Surgery, Division of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Tao Yuan, Taiwan. jacobpang@cgmh.org.tw
Weng
Wen-Hui
WH
Flores-Morales
Amilcar
A
Johansson
Björn
B
Pourian
Mohammad R
MR
Nilsson
Peter
P
Pousette
Ake
A
Larsson
Catharina
C
Norstedt
Gunnar
G
D000728:Androgens / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D000077209:Decitabine; D018450:Disease Progression; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000032:analysis / Q000037:antagonists & inhibitors; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032681:Spectral Karyotyping
D000728:Androgens; C000717967:DNMT3A protein, human; D000077209:Decitabine; D008780:Methyltransferases; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C112218:TRDMT1 protein, human; D001374:Azacitidine