Peripheral-type benzodiazepine receptors in the regulation of proliferation of MCF-7 human breast carcinoma cell line

Peripheral-type benzodiazepine receptors (PBR) have been implicated in cell proliferation. The aim of the present study was to test the effect of the PER ligands PK 11195 and Ro 5-4864 and the central-type benzodiazepine receptor ligand clonazepam on breast carcinoma cell proliferation, using [H-3] thymidine incorporation. We then carried out a study to identify where the PER-specific ligands Ro 5-4864 and PK 11195 act in the fell cycle, using flow cytometric analysis. We found PER expression in the malignant breast cancer tumors, representing various levers of estrogen and/or progesterone receptors, as well as in the MCF-7 breast carcinoma cell line. PK 11195 and Ro 5-4864 inhibited cell proliferation at concentrations of 10(-5) to 10(-4) M, while clonazepam (the central-type benzodiazepine receptor-specific ligand) had no effect. In this same concentration range, PK 11195 and Ro 5-4864, in contrast to clonazepam, induced an accumulation of MCF-7 cells in both the G(0)-G(1) and G(2)-M phases of the cell cycle. The present study demonstrates that PER ligands play a role in regulating cell proliferation in the human breast carcinoma cell line MCF-7. (C) 1999 Elsevier Science Inc.