The Role of Estrogen Regulated Secreted Proteins for Growth Regulation of Human Breast Cancer

Abstract

Breast cancer is the most common cancer disease among women in the western countries. The female sex hormone estradiol plays an important role in the etiology of the disease as a promoter for the growth of initiated cells and as a promotor for growth of the established tumor cells. A prerequisite for estrogen stimulated cell proliferation is presence of estrogen receptors in the tumor cells, and about 60% of the primary breast tumors contain estrogen receptors. About 33% of the breast cancer patients with advanced disease respond to endocrine treatments as antiestrogen or estrogen ablation treatments, indicating the very important role of estrogens even in the metastatic disease (1,2,3,4). The mechanisms by which estrogen stimulates cell proliferation of breast cancer cells have been extensively studied and autocrine or paracrine mechanisms have been indicated in several studies (5,6,7,8). Regulation of cell proliferation by autocrine factors with a negative growth effect has also been shown (9,10); and estradiol (E2) stimulation of human breast cancer cell lines has been suggested to arise from upregulation of positive factors as well as down regulation of negative factors (11,12). Examples of factors shown to have a growth stimulatory effect on breast cancer cells are insulin, IGF-I, IGF-II, EGF and TGF-α (11,13,14,15), whereas TGF-β has been found to have a negative effect on cell proliferation (9). At present much information is available on factors involved in E2-regulated growth of breast cancer cells, but the regulation seems to be complex and more information is still required to be able to develop new strategies in the treatment of E2-dependent breast tumor growth.