Calmodulin Antagonism By Antiestrogens In Breast Cancer Cells.

We have studied the effect of several derivatives of the triphenylethylene antiestrogen family on the inhibition of both calmodulin (CaM)-dependent cyclic 3&s;:5&s;-monophosphate-phosphodiesterase (cAMP-PDE) activity and proliferation of breast cancer cells. Tamoxifen (TAM) is an effective antagonist of CaM in the activation of PDE extracted from MCF-7 cells. Hydroxylation of the antiestrogen molecule significantly decreases its ability to antagonize CaM in vitro. Furthermore, the estrogen - independent growth inhibiting activity of several antiestrogens and other CaM antagonists correlated with their antagonistic effects on CaM activity. Our data suggest that antiestrogen interactions with CaM may play a role in mediating the drug-induced estrogen-independent inhibition of breast cancer cell growth.