P21 - A MONITOR OF P53 DYSFUNCTION IN OVARIAN NEOPLASIA

p53 is an important tumor suppressor gene which is activated in respon se to DNA damage. The induced expression of p53 causes either cell cyc le G1 arrest or apoptosis. The recently cloned p21 gene (WAF1/CIP1/SDI 1) is known to be directly activated by wild-type but not mutant p53 a nd can suppress the growth of human cells in G1 by inhibiting the acti vity of cyclin-dependent kinases (CDKs). As p21 is activated by p53 an d is a negative regulator of the cell cycle, it is possible that p21 c ould be a sensitive marker to monitor p53 function. To investigate the mRNA expression level and mutation status of p53 and p21 genes, quant itative polymerase chain reaction (PCR) and direct cDNA sequence analy sis were performed. mRNA expression levels of p53 and p21 genes relati ve to the beta-tubulin gene were examined in 32 ovarian tumors (24 car cinomas, six low malignant potentials (LMPs), two benigns) and six nor mal ovaries. Of 13 ovarian tumors with p21 underexpression, nine p53 m utated cases (69%) and one polymorphism case were found. Among nine p5 3 mutated cases, three cases showed p53 overexpression, another three cases showed p53 underexpression and a further three cases showed norm al expression of p53. These findings suggest that mRNA underexpression of p21 may be a more useful indicator of p53 dysfunction than mRNA ex pression of p53.