PMID- 11172899 OWN - NLM STAT- MEDLINE DCOM- 20010322 LR - 20191210 IS - 0165-4608 (Print) IS - 0165-4608 (Linking) VI - 124 IP - 2 DP - 2001 Jan 15 TI - Comparison of the malignant phenotype and genotype of the human androgen-independent cell line DU 145 and a subline derived from metastasis after orthotopic implantation in nude mice. PG - 98-104 AB - To investigate the potential genetic changes underlying the progression of human hormone-resistant prostate cancer, we related chromosomal alterations of the DU 145 cell line and a subline isolated form a metastasis in an orthotopic model to tumorigenicity, metastasis and chemoresistance. In 15 mice 1 x 10(5) DU 145 cells were injected into the dorsal prostate. From a resulting paraaortic lymphnode metastasis, we isolated a subline (DU 145 MN1), which was injected into 15 nude mice. The sulforhodamine B (SRB) assay was used to analyze cell doubling time and the IC(50) of cisplatin and 5-fluorouracil for both cell lines. Cytogenetic characterization was performed with conventional karyotype analysis and fluorescence in situ hybridization (FISH). After orthotopic implantation of DU 145 cells tumorigenicity was 100% whereas only 2 mice revealed lymphnode metastases. In contrast, the take rate after implantation of DU 145 MN1 was 100%, with lymphnode metastases in 7 mice. The SRB assay revealed a 8-fold increased IC(50) for cisplatin and a 2.5-fold increase for 5-FU in DU 145 MN1 as compared to DU 145 cells. There was gain of a chromosome 8 and only two copies of chromosome 17 in the DU 145 MN1 cells as compared to the parental cell line. The emergence of an i(9)(q10) in addition to two normal chromosome 9 homologues in the DU 145 MN1 cell line was confirmed by FISH using a chromosome 9-specific painting probe. In summary, clonal evolution of the chromosomal changes following repeated orthotopic implantation, may assist in locating the genes involved in the progression and chemoresistance of human hormone-resistant prostate cancer. FAU - Bex, A AU - Bex A AD - Clinic of Urology, University of Essen Medical School, 45122 Essen, Germany. FAU - Wullich, B AU - Wullich B FAU - Endris, V AU - Endris V FAU - Otto, T AU - Otto T FAU - Rembrink, K AU - Rembrink K FAU - Stockle, M AU - Stockle M FAU - Rubben, H AU - Rubben H LA - eng PT - Comparative Study PT - Evaluation Study PT - Journal Article PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 RN - 0 (Androgens) RN - 0 (Antineoplastic Agents) RN - Q20Q21Q62J (Cisplatin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Androgens/*metabolism MH - Animals MH - Antineoplastic Agents/pharmacology MH - Brain Neoplasms/*genetics/pathology/*secondary MH - Cell Division/drug effects/genetics MH - Chromosome Aberrations MH - Cisplatin/pharmacology MH - Clone Cells MH - Cytogenetics MH - Drug Resistance, Neoplasm MH - Fluorouracil/pharmacology MH - Humans MH - Inhibitory Concentration 50 MH - Male MH - Mice MH - Mice, Inbred Strains MH - Mice, Nude MH - Neoplasm Transplantation MH - Prostatic Neoplasms/drug therapy/*genetics/*pathology MH - Tumor Cells, Cultured EDAT- 2001/02/15 11:00 MHDA- 2001/03/27 10:01 CRDT- 2001/02/15 11:00 PHST- 2001/02/15 11:00 [pubmed] PHST- 2001/03/27 10:01 [medline] PHST- 2001/02/15 11:00 [entrez] AID - S0165-4608(00)00332-0 [pii] AID - 10.1016/s0165-4608(00)00332-0 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 2001 Jan 15;124(2):98-104. doi: 10.1016/s0165-4608(00)00332-0.