title: Prostate cancer cells use genetic and epigenetic mechanisms for progression to androgen independence.
abstract: 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.
authors.affiliation: Urology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Horacio
authors.initials: H
authors.lastname: Murillo
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Schmidt
authors.forename: Melissa
authors.initials: M
authors.lastname: Karter
authors.forename: Kari A
authors.initials: KA
authors.lastname: Hafner
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kondo
authors.forename: Karla V
authors.initials: KV
authors.lastname: Ballman
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Tindall
mesh_terms: 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
chemical_list: D000728:Androgens; D004268:DNA-Binding Proteins; C104382:PLAG1 protein, human