Effects of different progestogens on human breast tumor cell growth

Abstract

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 E2 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.