title: Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.
abstract: The mammalian Cks family consists of 2 well-conserved small proteins, Cks1 and Cks2. Cks1 has been shown to promote cell-cycle progression by triggering degradation of p27(kip1). The function of Cks2 in somatic mammalian cells is not well understood although it is required for the first metaphase/anaphase transition during the meiosis. Emerging evidence shows that elevated expression of Cks1 and Cks2 is often found in a variety of tumors, and is correlated with poor survival rate of the patients. Here we demonstrated that expression of Cks1 and Cks2 were elevated in prostate tumors of human and animal models, as well as prostatic cancer cell lines. Forced expression of Cks1 and Cks2 in benign prostate tumor epithelial cells promoted cell population growth. Knockdown of Cks1 expression in malignant prostate tumor cells inhibited proliferation, anchorage-independent growth, and migration activities, whereas knockdown of Cks2 expression induced programmed cell death and inhibited the tumorigenicity. Collectively, the data suggest that elevated expression of Cks1 contributes to the tumorigenicity of prostate tumor cells by promoting cell growth and elevated expression of Cks2 protects the cells from apoptosis. Thus, the finding suggests a novel therapeutic strategy for prostatic cancer based on inhibiting Cks1 and Cks2 activity.
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030-3303, USA.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Lan
authors.forename: Yongyou
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Lin
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases / Q000235:genetics / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; D017489:CDC28 Protein Kinase, S cerevisiae; C083689:CKS2 protein, human; C474110:Cks1 protein, mouse; C474109:Cks2 protein, mouse; D018844:Cyclin-Dependent Kinases