Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer

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Abstract
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.