Somatostatin up-regulates topoisomerase II alpha expression and affects LNCaP cell cycle

mRNA differential display-PCR analysis was used to perform a systematic scr eening of Somatostatin (SS)-regulated genes in the human prostatic carcinom a cell line LNCaP (Lymph Node Carcinoma of the Prostate). A 170 bp fragment was shown to be up-regulated by SS. Sequence analysis of this fragment rev ealed its homology with the human Topoisomerase II Alpha gene. Up-regulatio n of Topoisomerase IT Alpha was confirmed by Northern blot hybridisation an d was induced by the same dose of SS (1 nM) earlier demonstrated to inhibit LNCaP cell growth. Furthermore, SS possible effects on timing, as well as concentration of Topoisomerase II Alpha along the different phases of the c ell cycle were investigated. To this purpose changes in the enzyme protein concentration in response to SS were assessed in synchronised LNCaP cells. The hormone was shown to exert a perturbing effect on both parameters consi dered, possibly related to its inhibitory action on LNCaP cell replication. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.