SUBCELLULAR-LOCALIZATION OF ACCUMULATED P53 IN OVARIAN-CANCER CELLS

Inactivation of the tumor suppressor gene p53 is frequently associated with ovarian cancer. Accumulation of stabilized p53 protein is a comm on feature in this tumor type. Underlying mutations in the p53 core re gion can lead to loss of the normal conformational state or loss of re sidues necessary for DNA binding and transcriptional regulation, Five HPV-free ovarian cancer cell lines established in our laboratory with and without immunocytochemically detectable p53 expression were select ed for the correlation of subcellular localization of aberrant p53 and the type of gene mutation. The expression level regarding staining in tensity and proportion of cells accumulating p53 was characterized emp loying an immunoreactive score. Two cell lines with point missense mut ations in the core region showed strong nuclear or nuclear plus cytopl asmic staining. One cell line with exclusive staining of the cytoplasm contained a deletion of the major nuclear localization signal. Among two cell lines without p53 accumulation, one contained a microdeletion resulting in a frame shift, the other carried the wild-type sequence. The MDM2 oncogene was not amplified and its gene product was not over expressed, In ovarian cancer, inactivated p53 can accumulate in both m ajor cell compartments depending on the type of the underlying mutatio n. (C) 1996 Academic Press, Inc.