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Inhibition of growth and induction of apoptosis by androgens of a variant of LNCaP cell line
Authors:Joly-Pharaboz M O  Ruffion A  Roch A  Michel-Calemard L  André J  Chantepie J  Nicolas B  Panaye G
Institution:

a INSERM-U 329 Hôpital Debrousse, 29 Rue Soeur Bouvier, 69322 Lyon Cédex 05, France

b Hospices Civils de Lyon, Lyon, France

c Université Claude-Bernard Lyon I., Lyon, France

Abstract:Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100 000 binding sites/cell, KD for 5greek small letter alpha dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17β-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to ≈40% of controls. ED70s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased 3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors’ knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
Keywords:LNCaP cell line  Androgens  Apoptosis
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