title: Comprehensive genotypic analysis of human prostate cancer cell lines and sublines derived from metastases after orthotopic implantation in nude mice.
abstract: We recently reported on a prostate cancer progression model which was based on repeated orthotopic implantation of human prostate cancer cell lines into athymic nude mice leading to an increase of tumor cell aggressiveness. To assess progression-associated clonal evolution of genotypic changes, we now performed comparative cytogenetic characterization of the original cell lines DU145 and PC3 with derived sublines DU145MN1 and PC3-N. Cell line PC3-125-1L, isolated from a lung metastasis after subcutaneous inoculation of PC3 into nude mice, was included in the study. Whole-genome analysis was performed using spectral karyotyping and comparative genomic hybridization. Fluorescence in situ hybridization was used to assess amplification of selected genes, which are supposed to play a role in prostate cancer progression. Differences in the genetic constitution between parental cell lines and sublines involved gains of genetic material at 2q, 5q, 12p/q, and 18p as well as losses at 6p, 7q, 17p, 18q, and 22q. Loss of 17p in DU145MN1 and high-level amplification of MYC in PC3-125-1L resulted in loss of p53 expression and upregulation of Myc expression, respectively, as was assessed by Western blotting. Thus, the nude mice model is very useful to follow clonal evolution of genetic changes during increase of prostate cancer aggressiveness and possibly to clone genes associated with the progression of prostate cancer.
authors.affiliation: Department of Urology and Pediatric Urology, University of the Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Lensch
authors.forename: Claudia
authors.initials: C
authors.lastname: Götz
authors.forename: Christine
authors.initials: C
authors.lastname: Andres
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Zwergel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Unteregger
authors.forename: Jörn
authors.initials: J
authors.lastname: Kamradt
authors.forename: Michael
authors.initials: M
authors.lastname: Stoeckle
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002869:Chromosome Aberrations; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D011471:Prostatic Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D016159:Tumor Suppressor Protein p53