Comprehensive genotypic analysis of human prostate cancer cell lines and sublines derived from metastases after orthotopic implantation in nude mice.
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.
Lensch
Ramona
R
Department of Urology and Pediatric Urology, University of the Saarland, D-66421 Homburg/Saar, Germany.
Götz
Claudia
C
Andres
Christine
C
Bex
Axel
A
Lehmann
Jan
J
Zwergel
Thomas
T
Unteregger
Gerhard
G
Kamradt
Jörn
J
Stoeckle
Michael
M
Wullich
Bernd
B
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
D016159:Tumor Suppressor Protein p53