Expression of p21 and p53 in rat gingival and human oral epithelial cells after cyclosporine A treatment.
OBJECTIVE
Expression of p21 and p53 were examined, at gene and protein levels, in edentulous gingival epithelial cells from rats and from a human oral epidermoid carcinoma cell line, OECM1, after cyclosporine A therapy.


METHODS
In vivo: 20 partially edentulous SD rats were assigned into cyclosporine A feeding and control groups. After the rats were killed, p21 and p53 in gingiva were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. In vitro: after cyclosporine A treatment, p21 and p53 of OECM1 cells were evaluated by western blot and the luciferase assay. The distribution of OECM1 cells in each phase of the cell cycle was evaluated by flow cytometry.


RESULTS
The mRNA expression of p21 was significantly higher in the cyclosporine A group than in the control group. A greater number of positive anti-p21-stained cells were observed in the gingival epithelium of the cyclosporine A group than in the control group. Significantly higher levels of p21 protein and activity were observed in OECM1 cells after cyclosporine A treatment than in cells without treatment. A relative increase of cells in G0/G1 phases, and a decrease of cells in G2/M phases, were observed in OECM1 cells after cyclosporine A treatment.


CONCLUSIONS
In the present study, higher p21 mRNA and protein expressions were observed after cyclosporine A treatment. Thus, an up-regulation of p21 expression, via a p53-independent pathway, by cyclosporine A in gingival and oral epithelial cells was suggested.
Tu
H-P
HP
Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan, China.
Fu
E
E
Chen
Y-T
YT
Wu
M-H
MH
Cheng
L-C
LC
Yang
S-F
SF
D000818:Animals; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D016572:Cyclosporine / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects*; D005881:Gingiva / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007576:Jaw, Edentulous, Partially / Q000201:enzymology / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016572:Cyclosporine