Somatostatin up-regulates topoisomerase II alpha expression and affects LNCaP cell cycle.
mRNA differential display-PCR analysis was used to perform a systematic screening of Somatostatin (SS)-regulated genes in the human prostatic carcinoma 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 revealed its homology with the human Topoisomerase II Alpha gene. Up-regulation of Topoisomerase II Alpha was confirmed by Northern blot hybridisation and 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 cell 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 considered, possibly related to its inhibitory action on LNCaP cell replication.
Brevini-Gandolfi
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TA
Centre for Endocrinological Oncology, Department of Endocrinology, University of Milan, Milan, Italy. tiziana.brevini@unimi.it
Cillo
F
F
Favetta
L A
LA
Montagna
A
A
Motta
M
M
D000951:Antigens, Neoplasm; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D013004:Somatostatin; D004250:DNA Topoisomerases, Type II