Susceptibility of human breast epithelial cells in vitro to hormones and drugs

Abstract

Breast cancer is often hormone responsive with growth or regression of tumors modulated by endocrine manipulations. Estrogens are known to control the growth of many mammary carcinomas in experimental animals, and humans. Knowledge of tumor response to hormones will greatly improve the ability to plan therapy for breast cancer patients. Chemoprevention of breast cancer has been mostly aimed at reducing the rate of cell division through administration of anti-hormones. Tamoxifen has shown to be species, tissue, and cell-type specific. Cell proliferation in mammary gland occurs in a non-random fashion since there are specific compartments with varied rates of proliferation represented by the terminal end buds that are ready for differentiation into alveolar buds. The aim of this work was to study the effect of 17beta estradiol as well as an antiestrogen, tamoxifen in several in vitro systems to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions. Normal, benign lesions, and duct carcinomas of human breast tissues were processed for organ culture. In the case of the normal breast tissue it was enzymatically digested and culture as organoid culture as well. Several immortalized normal and malignant human breast cell lines were also used in these studies to analyze the effect of 17beta estradiol, progesterone, tamoxifen and anti-progestin RU486. Both 17beta estradiol and progesterone stimulated cell proliferation whereas tamoxifen and RU486 inhibited such effect under these experimental conditions. Thus, in vitro systems allowed to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions.