Changes in expression of cell-cycle-related genes in PC-3 prostate cancer cells caused by ovine uterine serpin.
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.
Padua
Maria B
MB
Department of Animal Sciences, University of Florida, Gainesville, Florida 32611-0910, USA.
Hansen
Peter J
PJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015842:Serine Proteinase Inhibitors; D015843:Serpins / Q000494:pharmacology*; D012756:Sheep; D015854:Up-Regulation; D014599:Uterus / Q000737:chemistry*
D015842:Serine Proteinase Inhibitors; D015843:Serpins