A novel anti-proliferative property of clusterin in prostate cancer cells.
Clusterin is a ubiquitous secretory glycoprotein that is known to suppress certain forms of apoptosis. Since apoptosis and proliferation are two opposing cellular events, it remains unclear if clusterin has any effect on cellular proliferation. The objective of the present study was to examine the effects of clusterin on proliferation in a prostate cancer cell line, LNCaP. We found that clusterin inhibited EGF-mediated proliferation in these cells, as measured by (3)H-thymidine incorporation and by cell counting. Clusterin did not bind with EGF nor did it block phosphorylation of the EGF receptor. Treatment of LNCaP cells with EGF resulted in a transient increase in the expression of both c-Fos and c-Jun. Addition of clusterin to these cultures significantly down-regulated the protein level of c-Fos, but not c-Jun. These results demonstrated a novel biological role for clusterin. Clusterin is not only anti-apoptotic but also anti-proliferative. The anti-proliferative event maybe associated with a down-regulation of c-Fos.
Zhou
Wei
W
Department of Urology, Tarry 11-715, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Janulis
Lynn
L
Park
Irwin I
II
Lee
Chung
C
D002455:Cell Division / Q000187:drug effects; D051152:Clusterin; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D066246:ErbB Receptors / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000494:pharmacology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D006131:Growth Inhibitors; D018832:Molecular Chaperones; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors