Role of cathepsin D in prostatic cancer cell growth and its regulation by brefeldin A |
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Authors: | Konno S Cherry J P Mordente J A Chapman J R Choudhury M S Mallouh C Tazaki H |
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Affiliation: | (1) Department of Urology, New York Medical College, Munger Pavilion 4th Floor, Valhalla, NY 10595, USA e-mail: sensuke_konno@nymc.edu Tel.: +1-914-5943745; Fax: +1-914-5944394, US |
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Abstract: | We investigated a possible relationship between brefeldin A (BFA), an antibiotic, and cathepsin D (Cat.D), a lysosomal protease, in prostate cancer proliferation. Effects of BFA (30 ng/ml) were examined on the growth of three human prostatic cancer cell lines, PC-3, DU-145, and LNCaP cells. Its effect on Cat.D in these cancer cells was assessed by Western blots and compared with Cat.D expressed in clinical prostate specimens (n=55). BFA profoundly (>70%) inhibited the growth of all three cancer cell lines. Western blots revealed that expression of procathepsin D (Pro.Cat.D) was markedly increased with BFA, whereas actively proliferating (control) cells greatly exhibited mature Cat.D. Analysis of prostate specimens then showed predominant Pro.Cat.D expression in non-cancerous tissues while also showing enhanced expression of mature Cat.D in all cancer specimens. Therefore, BFA-induced growth inhibition in prostatic cancer cells is associated with a blocking of Cat.D maturation (activation), suggesting a possible role of Cat.D in prostate cancer proliferation/development. |
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Keywords: | Cathepsin D Brefeldin A Prostate cancer |
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