|
|
Molecular
response of human glioblastoma multiforme cells to ionizing radiation: cell
cycle arrest, modulation of the expression of cyclin-dependent kinase
inhibitors, and autophagy
Yao KC,
Komata T, Kondo Y, Kanzawa T, Kondo S, Germano IM
Department
of Neurosurgery, Mount Sinai School of Medicine, New York, New York, USA
Object.
Ionizing radiation is the gold-standard adjuvant treatment for glioblastoma
multiforme (GBM), the most aggressive primary brain tumor.
The mechanisms underlying neoplastic glial cell growth inhibition after
administration of ionizing radiation, however, remain largely unknown.
In this report, the authors characterize the response of GBM cells to ionizing
radiation and elucidate factors that correlate with the radiosensitivity of
these tumors.
Methods.
Six human GBM cell lines were subjected to increasing doses of radiation.
Each demonstrated a dose-dependent suppression of cell proliferation.
In the most radiosensitive cell line, the authors demonstrated a transient
increase in the expression of the cyclin-dependent kinase inhibitors (CDKIs) p21
and p27, which corresponded with a G1 cell-cycle arrest.
In contrast, the most radioresistant cell line demonstrated a decrease in p21
and p27 expression levels, which correlated with a failure to arrest.
Apoptosis did not occur in any cell line following irradiation.
Instead, autophagic cell changes were observed following administration of
radiation, regardless of the relative radiosensitivity of the cell line.
Conclusions.
These findings elucidate some of the molecular responses of GBMs to irradiation
and suggest novel targets for future therapy.
PMID: 12593626 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12593626&dopt=Abstract |
