The effect of tibolone on proliferation, differentiation and apoptosis in normal breast cells

Abstract

Tissue homeostasis is the result of a balance between proliferation, differentiation and apoptosis, with apoptosis, or spontaneous programmed cell death, being thought to play a major role in the growth and regulation of both normal and tumor tissue. The expression of bcl-2protein plays an important role in controlling apoptosis, and this protein has been shown to be influenced by fluctuations in hormone levels during the menstrual cycle. Although considerable work has been carried out investigating the effect of estrogens on normal breast cells and breast cancer cell lines, less is known about the effect of progestins, and very little has been published on the tissue-specific hormone tibolone, which exhibits estrogenic, progestogenic and androgenic characteristics. Studies with tibolone, using normal human breast epithelium cells, demonstrate that this hormone displays a progestin-likeprofile and has favorable effects with respect to breast tumorigenesis. Tibolone decreases cell proliferation rates, promotes 17ß-hydroxysteroid dehydrogenase activity (a marker of epithelial cell differentiation) and increases apoptosis in normal as well as breast cancer cells. These findings indicate a possible future role for tibolone in the treatment of breast cancer and the need for further detailed investigations.

Key Words:

• APOPTOSIS
• BREAST CELLS
• BCL-2 EXPRESSION