Influence of ionizing radiation on proliferation, c-myc expression and the induction of apoptotic cell death in two breast tumour cell lines differing in p53 status

Purpose : To determine the capacity of ionizing radiation to inhibit proliferation, to suppress c- myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB231 cell line. Materials and methods : Growth inhibition and cell killing were determine...

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Bibliographic Details
Published in:	International journal of radiation biology Vol. 72; no. 5; pp. 547 - 559
Main Authors:	WATSON, N. C, DI, Y.-M, ORR, M. S, FORNARI, F. A, RANDOLPH, J. K, MAGNET, K. J, JAIN, P. T, GEVIRTZ, D. A
Format:	Journal Article
Language:	English
Published:	London Informa UK Ltd 01-11-1997 Taylor & Francis
Subjects:	Apoptosis - radiation effects Biological and medical sciences Biological effects of radiation Breast Neoplasms - genetics Breast Neoplasms - pathology Cell Division - radiation effects DNA Damage Female Fundamental and applied biological sciences. Psychology G1 Phase Genes, myc - radiation effects Humans Radiocontamination Space life sciences Tissues, organs and organisms biophysics Tumor Cells, Cultured Tumor Suppressor Protein p53 - analysis Ionizing radiation DNA Established cell line Radiation injury Tumor Gene expression Apoptosis
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Summary:	Purpose : To determine the capacity of ionizing radiation to inhibit proliferation, to suppress c- myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB231 cell line. Materials and methods : Growth inhibition and cell killing were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent endlabelling. c- myc expression was monitored by Northern blotting. Results : Inhibition of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G2 while MCF-7 cells accumulated in both the G1 and G2 phases of the cell cycle after irradiation. There was no evidence of apoptosis in either cell line. In MCF-7 cells, growth inhibition correlated closely with an early dose-dependent suppression of c- myc expression; in MDA-MB231 cells, there was no correspondence between growth inhibition and a transient, dose- independent reduction in c- myc message. Conclusions : These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c- myc may be linked to the DNA damage response pathway, neither p53 nor c- myc are essential for growth arrest in response to ionizing radiation.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0955-3002 1362-3095
DOI:	10.1080/095530097143059