Τίτλος:
Cell senescence and a mechanism of clonal evolution leading to
continuous cell proliferation, loss of heterozygosity, and tumor
heterogeneity: Studies on two immortal colon cancer cell lines
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Extensive karyotypic analysis was performed on early and late passages
of two continuous human cell lines, SW480 and SW620, that were derived
from the same colon cancer patient. We cultivated these two cell lines
in vitro for a period of 24 months and periodically examined their
chromosome constitution. SW480 cells, from passage 138, were injected
subcutaneously into 20 nude mice. The tumors that grew in nude mice were
then cultivated in vitro for several passages to compare histopathologic
findings and tumor growth patterns with clonal chromosomal profiles.
Despite some karyotypic diversity, the two cell lines exhibited common
marker chromosomes and followed similar patterns of evolution. During
subsequent passages, acquisition of new chromosomal abnormalities gave
rise to sidelines with a near-diploid genome that frequently underwent
endoreduplication. Genomic instability seemed to play an important role
in the emergence, growth, and subsequent elimination of the heterogenous
sidelines by selection, clonal expansion, and cell death by senescence.
Despite continuous growth, both the cell lines occasionally showed
telomeric associations and random dicentric and multicentric formations.
These lesions were considered evidence of cell senescence and were
related to the disappearance of particular sidelines through evolution.
Successful evolutionary steps were characterized by elimination of
pre-existing marker chromosomes that were subsequently replaced in the
karyotype by their cytologically intact homologous chromosomes possibly
after selective endoreduplication. Frequent loss of heterozygosity for
the chromosomes taking part in this process is postulated. We suggest
that one of the mechanisms by which cancer cells bypass senescence may
be related to their potential for continuous clonal diversification.
Συγγραφείς:
Gagos, S
Iliopoulos, D
TseleniBalafouta, S
Agapitos, M and
Antachopoulos, C
Kostakis, A
Karayannakos, P
Skalkeas, G
Περιοδικό:
CANCER GENETICS AND CYTOGENETICS
Εκδότης:
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI:
10.1016/S0165-4608(96)00049-0
