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Characteristics of the Biphasic Action of Androgens and of the Potent Antiproliferative Effects of the New Pure Antiestrogen EM-139 on Cell Cycle Kinetic Parameters in LNCaP Human Prostatic Cancer Cells¹

Medical Research Council of Canada Group in Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, G1V 4G2, Canada

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e., dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G₀-G₁ fraction with a corresponding increase of the S and G₂ + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G₀-G₁ fraction at the expense of the S and especially the G₂ + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.

¹ This research was supported in part by the Medical Research Council of Canada (Group in Molecular Endocrinology), the Fonds de la Recherche en Santé du Québec, and Endorecherche.

² Holder of a postdoctoral fellowship from the Medical Research Council of Canada.

³ Holder of a scholarship from the Medical Research Council of Canada.

⁴ To whom requests for reprints should be addressed, at Laboratory of Molecular Endocrinology, CHUL Research Center, 2705 Laurier Boulevard, Quebec, QC, G1V 4G2, Canada.

Received 3/22/91. Accepted 7/15/91.

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