Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells.
BACKGROUND
Inactivation of p53 by binding to simian virus 40-T antigen (SV40-T) and human papilloma virus type 16 protein E6 (HPV 16 E6) in transfected human diploid fibroblasts causes enhanced radioresistance. The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines.


METHODS
The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: upregulation in C4-1, downregulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay.


RESULTS
Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance.


CONCLUSIONS
In C4-1 and SW 756 cells, treatment with dexamethasone induces radioresistance, and changes in expression levels of HPV 18 genes E6 and E7 do not correlate with the changes in radiosensitivity. Dexamethasone-induced radioresistance has previously been observed in HeLa cells, another human cervical carcinoma cell line. This leads us to speculate that dexamethasone-induced radioresistance may be important in certain clinical situations, and that therefore, the phenomenon deserves further study.
Rutz
H P
HP
Laboratoire de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne.
Mariotta
M
M
von Knebel Doeberitz
M
M
Mirimanoff
R O
RO
D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects*; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis*; D027383:Papillomaviridae / Q000235:genetics*; D011836:Radiation Tolerance / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D003907:Dexamethasone