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Changes in expression of cell-cycle-related genes in PC-3 prostate cancer cells caused by ovine uterine serpin.

Abstract
The hormonal-regulated serpin, ovine uterine serpin (OvUS), also called uterine milk protein (UTMP), inhibits proliferation of lymphocytes and prostate cancer (PC-3) cells by blocking cell-cycle progression. The present aim was to identify cell-cycle-related genes regulated by OvUS in PC-3 cells using the quantitative human cell-cycle RT(2) Profiler PCR array. Cells were cultured +/-200 microg/ml recombinant OvUS (rOvUS) for 12 and 24 h. At 12 h, rOvUS increased expression of three genes related to cell-cycle checkpoints and arrest (CDKN1A, CDKN2B, and CCNG2). Also, 14 genes were down-regulated including genes involved in progression through S (MCM3, MCM5, PCNA), M (CDC2, CKS2, CCNH, BIRC5, MAD2L1, MAD2L2), G(1) (CDK4, CUL1, CDKN3) and DNA damage checkpoint and repair genes RAD1 and RBPP8. At 24 h, rOvUS decreased expression of 16 genes related to regulation and progression through M (BIRC5, CCNB1, CKS2, CDK5RAP1, CDC20, E2F4, MAD2L2) and G(1) (CDK4, CDKN3, TFDP2), DNA damage checkpoints and repair (RAD17, BRCA1, BCCIP, KPNA2, RAD1). Also, rOvUS down-regulated the cell proliferation marker gene MKI67, which is absent in cells at G(0). Results showed that OvUS blocks cell-cycle progression through upregulation of cell-cycle checkpoint and arrest genes and down-regulation of genes involved in cell-cycle progression.
AuthorsMaria B Padua, Peter J Hansen
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 107 Issue 6 Pg. 1182-8 (Aug 15 2009) ISSN: 1097-4644 [Electronic] United States
PMID19530225 (Publication Type: Journal Article)
Copyright(c) 2009 Wiley-Liss, Inc.
Chemical References
  • Serine Proteinase Inhibitors
  • Serpins
Topics
  • Animals
  • Cell Cycle (drug effects, genetics)
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Profiling (methods)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Male
  • Prostatic Neoplasms (drug therapy, genetics, pathology)
  • Serine Proteinase Inhibitors
  • Serpins (pharmacology)
  • Sheep
  • Up-Regulation
  • Uterus (chemistry)

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