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 rece ptor 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 fl ow cytometric analysis. We found PER expression in the malignant breast can cer tumors, representing various levers of estrogen and/or progesterone rec eptors, 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 liga nd) 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 demon strates that PER ligands play a role in regulating cell proliferation in th e human breast carcinoma cell line MCF-7. (C) 1999 Elsevier Science Inc.