PMID- 10942801
OWN - NLM
STAT- MEDLINE
DCOM- 20000908
LR  - 20190816
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 120
IP  - 2
DP  - 2000 Jul 15
TI  - Stepwise genetic changes associated with progression of nontumorigenic HPV-18 
      immortalized human prostate cancer-derived cell line to a malignant phenotype.
PG  - 117-26
AB  - Cytogenetics, fluorescence in situ hybridization (FISH), and comparative genomic 
      hybridization (CGH) were used to identify genes that are involved in the 
      development and progression of prostate cancer. For that purpose, we chose a cell 
      line established in vitro from a prostatic adenocarcinoma which was 
      nontumorigenic in nude mice and followed its progression to a tumorigenic cell 
      line. Stepwise changes were observed in the cell line as it became tumorigenic. 
      The composite karyotype at the nontumorigenic stage (CA-HPV-10) was 68 
      approximately 77,XXY,-(1, 9, 13, 14, 19, 22),+(4, 5, 11, 18, 20, 21),+(del(1) 
      (q23q31)=M1 (two copies), +der(9)t(1;9)(q24 approximately q31;p23)=M5(two 
      copies), der(14)t(14;?)(q10;?)=M17 in the majority of metaphases. These two 
      derivative chromosomes were also observed a previous study. Our CGH analysis 
      clearly showed that this deleted region in M1 is, in fact, translocated with 
      derivative M5 and, in reality, is amplified. The cell line established from 
      nodule (SCID 5019 p11), showed a number of new changes, as described; however, 
      the most significant change was amplification of the 8q23 approximately qter 
      region, harboring c-myc. This region was translocated with chromosomes 2, 4, and 
      16 as der(2)t(2;8)(q33;q23)=M12, der(4)t(4;8)(q34;q23)=M11, and 
      der(16)t(8;16)(q24;q21)=M9. We deduce from our study that amplification of c-myc 
      and other genes in the 8q23 approximately qter region were important in 
      progression but did not lead to tumorigenicity. The population that became 
      tumorigenic (SCID 5019 II) showed almost all of the same changes in the karyotype 
      as observed in the nodular cell line; the only significant change was the 
      appearance of der(11)t(4;11)(q32;q22)=M7 and the addition of another copy of 
      t(3q;7p)=M2. These new changes lead to loss of chromosomes 3p, 4pter 
      approximately q34, 6, 7q21 approximately qter, 11q22 approximately qter, and 18q, 
      and gain of 3q, 7p, 8q23 approximately qter, and 11pter approximately q22, before 
      the cell line became tumorigenic. The clonal selection of the population is 
      proven by the presence of a number of the same derivative chromosomes in both the 
      nodular and tumorigenic cell line. As it progressed to tumorigenicity, some of 
      the same changes observed in the original study re-appear at different stages of 
      malignancy, although it was absent in the nontumorigenic cell line. These are: 
      der(16)t(8;16)(q24;q21)=M9 in the nodular cell line and 
      der(11)t(4;11)(q32;q22)=M7 in the tumorigenic cell line. In our system, 
      amplification of c-myc and other genes in der(2)t(2;8)(q33;q23)=M12,der(4) 
      t(4;8)(q34;q23)=M11 together with the presence of der(16)t(8;16)(q24;q21)=M9 and 
      der(11)t(4;11)(q32;q22)=M5 makes the cell line tumorigenic. It is either 
      nontumorigenic, with the presence of a marker equivalent to der(16)=M9 and 
      der(11)=M7 observed in the original study, and only nodular (SCID 5019 p11, 
      present study), with the presence of number of markers with c-myc amplification 
      (M9, M11, and M12). There is accumulation of all the above-mentioned changes in 
      the same cell before it becomes tumorigenic.
FAU - Hukku, B
AU  - Hukku B
AD  - Cell Culture Laboratory, Children's Hospital of Michigan, Detroit 48201-2196, 
      USA.
FAU - Mally, M
AU  - Mally M
FAU - Cher, M L
AU  - Cher ML
FAU - Peehl, D M
AU  - Peehl DM
FAU - Kung, H
AU  - Kung H
FAU - Rhim, J S
AU  - Rhim JS
LA  - eng
GR  - N0I-CB33063/CB/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
SB  - IM
MH  - Aneuploidy
MH  - Animals
MH  - Cell Line, Transformed
MH  - Cell Transformation, Neoplastic/*genetics
MH  - *Cell Transformation, Viral
MH  - Chromosome Deletion
MH  - Cytogenetic Analysis
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Nucleic Acid Hybridization
MH  - Papillomaviridae/*growth & development
MH  - Phenotype
MH  - Prostatic Neoplasms/*genetics/pathology
MH  - Translocation, Genetic
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 2000/08/16 11:00
MHDA- 2000/09/19 11:01
CRDT- 2000/08/16 11:00
PHST- 2000/08/16 11:00 [pubmed]
PHST- 2000/09/19 11:01 [medline]
PHST- 2000/08/16 11:00 [entrez]
AID - S0165460800002168 [pii]
AID - 10.1016/s0165-4608(00)00216-8 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2000 Jul 15;120(2):117-26. doi: 
      10.1016/s0165-4608(00)00216-8.