Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression.
Clusterin is a highly conserved, widely distributed glycoprotein whose biological significance is still debated. Involved in many biological processes and disease states, clusterin is induced by cell injury and tissue regression, but is repressed during cell proliferation. We have previously reported that clusterin mRNA induction is associated with epithelial cell atrophy in the rat prostate and both clusterin transcript and protein accumulated in quiescent normal human skin fibroblasts. Here we show that transient clusterin overexpression, in SV40-immortalized human prostate epithelial cells (PNT2), resulted in increased accumulation of cells in the G(0)/G(1) phases of the cell cycle, accompanied by slowdown of cell cycle progression and decrease of DNA synthesis. The activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and the level of histone H3 mRNA (markers of cell proliferation) concomitantly decreased, while Gas1 mRNA (a marker of cell quiescence) accumulated. Thus it appears that clusterin, by opposing the effect of SV40 on the proliferation rate of PNT2 cells, acts as an anti-oncogene in the prostate, suggesting a role for this gene in controlling proliferation of normal and transformed prostate epithelial cells.
Bettuzzi
Saverio
S
Dipartimento di Medicina Sperimentale, Università di Parma, Via Volturno, 39-43100 Parma, Italy. saverio.bettuzzi@unipr.it
Scorcioni
Francesca
F
Astancolle
Serenella
S
Davalli
Pierpaola
P
Scaltriti
Maurizio
M
Corti
Arnaldo
A
D012437:Adenosylmethionine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism; D002472:Cell Transformation, Viral; D051152:Clusterin; D004261:DNA Replication; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013539:Simian virus 40 / Q000502:physiology
C495242:CLU protein, human; D018797:Cell Cycle Proteins; D051152:Clusterin; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C501181:Gas1 protein, rat; D006023:Glycoproteins; D006657:Histones; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase