실험적으로 유발된 흰 쥐 유방의 종양형성 과정에서 형태학적 변화에 따른 세포증식증 및 Apoptosis와의 관계

Abstract

Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoposis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogensis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7,12-dimethyl-benzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-β, Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 ㎎/㎖ DMBA by oral intubation) and control group. The results were as follows. 1, In the experimental group, breast tumors occurred twenty two of fifty nine rats(37.3%, 22/59) and the total number of was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompainied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced intraductal proliferation, and lowest ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the exent of its expression was less than 1% of all tumor cells ; 5. TGF-β was mainly expressed in the portion of tumor cell nests rather than in peripheral portion, and TGF-β immunoreactive tumor cells displayed good differentiation and did not reveal Brdu immunoreactivity. TGF-β labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the supperession of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis However the suppression of apoptosis is not related p53 muration, bcl-2, and TGF-β. TGF-β seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.