[The p53-p21(waf1) pathway and centrosome amplification in oral squamous cell carcinomas].
OBJECTIVE
To elucidate the possible role of p53-p21(waf1) pathway for centrosome amplification in oral squamous cell carcinoma (OSCC).


METHODS
Formalin-fixed, paraffin-embedded tissues of 8 cases of normal oral epithelium tissues and 27 cases of OSCC tissues were examined for the expression of p21(waf1) and mutated p53 proteins by flow cytometry and immunohistochemistry, and centrosome status was investigated by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The correlation between p21(waf1), p53 and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0.


RESULTS
All normal oral epithelium tissues showed normal centrosomes (1-2 centrosomes per cell)in epithelium cells, while 21 out of 27 cases (78%) of OSCC showed the evidence of centrosome amplification characterized by supernumerary centrosomes ( >2 centrosomes per cell) in a fraction of tumor cells. The quantity of p21(waf1) protein was lower in OSCC with centrosome amplification [(0.878 +/- 0.081)] than that in OSCC without centrosome amplification [(0.952 +/- 0.018), t = 3.838, P < 0.01], and negative correlations were found between the quantity of p21(waf1) protein and the degree of centrosome amplification (r = -0.472, P < 0.05), as well as the positive staining of p53 (r = -0.491, P < 0.01).


CONCLUSIONS
p53-p21(waf1) pathway might involve in centrosome duplication cycle in OSCC. Down-regulated p21(waf1) protein, via p53 transactivation-dependent mechanism, was likely a contributing factor towards centrosome amplification in OSCC.
Cai
Yang
Y
Department of Stomatology, Guiyang Medical College, Guiyang 550004, China. caiyang85@163.com
Liu
Yong-fa
YF
Yang
Hong
H
Lu
Hong
H
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018385:Centrosome / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53