抄録
Immunohistochemical investigations on the expression of PCNA, cyclin D1, and p53 were carried out on uterine proliferative lesions of heterozygous p53 deficient CBA mice [p53 (+/-) mice] given an intraperitoneal injection of 120 mg/kg body weight of N-ethyl-N-nitrosourea (ENU) followed by diet containing 1 or 2.5 ppm ethinylestradiol (EE) for 26 weeks. Histopathologically, uterine proliferative lesions were classified as endometrial stromal tumors (polyps and sarcomas), atypical hyperplasias (clear and basophilic cell types), an adenocarcinoma, and glandular hyperplasias. The PCNA labeling index (LI) for endometrial stromal tumors was very high in some areas of sarcomas in the ENU+EE groups, but very low elsewhere and in polyps, with significant differences. The PCNA LI for clear cell type atypical hyperplasias was also significantly greater than for glandular hyperplasias or basophilic cell type atypical hyperplasias. Values were comparable for each proliferative lesion between the ENU+2.5 ppm EE and ENU+1 ppm EE groups. In addition one adenocarcinoma with markedly high proliferation was seen with the higher dose of EE. Overexpression of cyclin D1 was also apparent in actively proliferating areas of stromal sarcomas and clear cell type atypical hyperplasia, percentages of positive cells being 67-100%. In contrast, p53 was only expressed in markedly proliferative areas of stromal sarcomas at percentages of 69 and 89 in the two groups. The present study indicates that cyclin D1 and p53 may play key roles in uterine transformation of proliferative lesions in p53 (+/-) mice.
