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.

Keyword

prostate cancer

androgen resistance

DNA microarray

spectral karyotype

CGH

comparative genomic hybridization

in-situ hybridization

cell-lines

genetic alterations

lncap-r

methylation

carcinoma

progression

proteins

family

Publication and Content Type

ref (subject category)

art (subject category)