CELL-PROLIFERATION AND APOPTOSIS DURING MAMMARY CARCINOGENESIS IN PITUITARY ISOGRAFTED MICE

In the present study, pituitary isografted animals serve as a model fo r evaluating the changes in differentiation, cell proliferation and pr ogrammed cell death (apoptosis) in mammary epithelial cells during car cinogenesis, The percentage of bromodeoxyuridine (BrdU)-labeled ductal and alveolar cells was significantly higher in pituitary isografted a nimals than in non-isografted control animals, BrdU-labeled cells incr eased in lobular hyperplastic nodules, keratinized nodules and mammary carcinomas; similar changes were observed with apoptotic cells, which were rare in mammary glands of adult non-isografted animals (one to t hree apoptotic cells per 2000 mammary epithelial cells), but their num ber increased in hyperplastic lesions and mammary carcinomas, Among hy perplastic nodular lesions, variants with high, moderate and low proli ferative activity and/or apoptotic cell death were identified, which s uggests that they may have different growth potentials and different p ropensities for malignant transformation. After removing pituitary iso grafts, apoptosis occurs in hyperplastic lesions but not in mammary ca rcinomas - implying that malignant tumors are hormone-independent. The dynamics of the changes in apoptotic cell death among various hyperpl astic lesions after removal of pituitary isografts suggests that these lesions are composed of heterogeneous cell populations, as far as the initiation of apoptosis is concerned, Our data indicate that apoptosi s can be used together with cell proliferation as a potential marker i n characterizing the growth potential and phenotypic diversity of hype rplastic, premalignant and malignant mammary gland lesions.