Effects of different progestogens on human breast tumor cell growth

Objective: To examine the effect of progestogens currently used in hormone therapy on growth of human breast tumor cells. Methods: MCF-7 cells were incubated in 10 nmol/l progestogens, including progesterone (P4), medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), and cyproterone acetate (CPA), with or without 17β-estradiol (E₂, 1 nmol/l and 10 nmol/l), as well as E₂ alone. Cell proliferation, apoptosis, and the expression of caspase-3 and proliferating cell nuclear antigen (PCNA) were evaluated. Results: The ratios of apoptosis : proliferation significantly increased in cultures with progestogens alone, 1 nmol/l E ₂ plus progestogens (except P4), and 10 nmol/l E₂ plus NETA. Caspase-3 significantly diminished in cultures with E2 alone; this was completely reversed when progestogens were added. MPA alone or with 1 nmol/l E₂ and 10 nmol/l E₂ plus NETA significantly increased caspase-3. Using progestogens alone, except P4, significantly decreased PCNA expression. Conclusions: The results demonstrate that various progestogens have different effects on growth of breast tumor cells, especially with the combined usage of E₂. Progestogen-induced apoptosis may be partly inhibited with the presence of E₂, but less severe with lower E₂ concentrations. Therefore, the choice of progestogens, as well as the doses of E₂ and/or progestogen, may influence breast cancer risk.