| Abstract |
Paired cell lines have been derived from tumor and adjacent normal tissue
from three prostate cancer specimens. These lines were immortalized with
genes from human papilloma virus. The line OPCT-1 was from a tumor sample
obtained from a 68 year old patient with TNM Stage T1cN0M0 and a Gleason
score of 6 (3+3). The OPCN-1 line was from the adjacent normal tissue of
this patient. The OPCT-2 and OPCN-2 lines were similarly derived from a 58
year old patient with T2aN0M0 and Gleason score of 5 (2+3). The OPCT-3 and
OPCN-3 lines were from a 54 year old patient with T3aN0M0 and Gleason
score of 4 (2+2). None of the patients received chemo-or hormonal therapy
before surgery. The doubling times of the OPCT-1 (1.1d) and OPCT-2 (1.8d)
lines in culture are shorter than those for their adjacent normal lines
(OPCN-1 = 2.7d; OPCN-2 = 2.9d). In contrast, the doubling time for OPCT-3
(2.1d) is not significantly different from that for OPCN-3 (2.3d). In a
methylcellulose-based clonogenic attachment-independent growth assay, only
the three tumor-derived lines formed colonies in these cultures,
indicating that they are tumor derived. The results of spectral karyotype
analysis from 10 mitotic figures each demonstrated variable chromosome
numbers and numerous aberrations (both clonal and non-clonal). OPCT-1 has
an average number of 49 (range = 48-50) chromosomes with trisomy 8, 9 and
20 observed for almost all mitotic figures, plus a chromosome 5 fragment.
Two clonal translocations were detected as t(3;8) and t(9;19). The range
of chromosome numbers was 60-86 for OPCT-2 and there were multiple
chromosomal fragments. Two clonal translocations were detected as t(1;3)
and t(4;5). For 7 out of 10 mitotic figures, non-clonal chromosomal
aberrations (translocations) were detected indicating an unstable genome.
The chromosome numbers of OPCT-3 vary from 62-110. Three clonal
translocations were detected as t(10;21), t(20;13) and dic(14;14). The
adjacent normal lines also had aberrant karyotypes with multiple
non-clonal aberrations. The range of chromosomes numbers were 59-84 for OPCN-1
with two clonal translocations [t(9;17) and t(9;19)], 78-94 for OPCN-2
with two clonal translocations [t(4;19) and t(19;4;19;4;19)], and 62-78
for OPCN-3 with four clonal translocations as [t(3;14), t(1;10;14), t(14;
15), and t(6;22)]. These results indicate that although the lines derived
from adjacent normal tissue are functionally different from the tumor
derived lines, the karyotype analysis indicates that they have a
considerable degree of genomic instability. This may reflect the inherent
diversity and heterogeneity of the cancerous prostate gland.
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