Prostate cancer cells use genetic and epigenetic mechanisms for progression to androgen independence.
Studies on the genetic basis of prostate cancer (PCa) have lead to mixed results with the only consensus being that PCa is a complex disease. Our goal was to gain insight into potential events involved in the acquisition of the androgen-refractory phenotype in PCa cells regardless of DNA-change dependence. To this end, we examined two LNCaP PCa cell line models of progression-one developed in vivo and one developed in vitro-using molecular cytogenetic and microarray gene expression analyses and extended this investigation of specific events into PCa tumors. The chromosomal changes observed in both in vivo and in vitro androgen-independent cell lines are similar to those seen in PCa during tumor progression. Correspondingly, gene expression analysis showed significant heterogeneity in the genes expressed among androgen-independent cells, but with some common gene expression changes that correlated with the acquired androgen-independent phenotype. Thus, growth conditions under which the cells progress appeared to impact the mechanisms used for progression, albeit within tumor-type-specific pathways. Our findings suggest that a dynamic and adaptable combination of epigenetic and DNA-change-dependent events can be used by PCa cells for the acquisition of the androgen-independent phenotype. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
Murillo
Horacio
H
Urology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Schmidt
Lucy J
LJ
Karter
Melissa
M
Hafner
Kari A
KA
Kondo
Yasushi
Y
Ballman
Karla V
KV
Vasmatzis
George
G
Jenkins
Robert B
RB
Tindall
Donald J
DJ
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002871:Chromosome Banding; D004268:DNA-Binding Proteins / Q000235:genetics; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D032681:Spectral Karyotyping
D000728:Androgens; D004268:DNA-Binding Proteins; C104382:PLAG1 protein, human