Bioscience, Biotechnology, and Biochemistry
Online ISSN : 1347-6947
Print ISSN : 0916-8451
Biochemistry & Molecular Biology Regular Papers
Tumor-Suppressive Lipoxygenases Inhibit the Expression of c-myc mRNA Coding Region Determinant-Binding Protein/Insulin-Like Growth Factor II mRNA-Binding Protein 1 in Human Prostate Carcinoma PC-3 Cells
Yuki KAWAKAMI, Noriyuki KUBOTA, Natsuki EKUNI, Toshiko SUZUKI-YAMAMOTO, Masumi KIMOTO, Hiromi YAMASHITA, Hideaki TSUJI, Tanihiro YOSHIMOTO, Mitsuo JISAKA, Junko TANAKA, Hirofumi F. FUJIMURA, Yoshihiro MIWA, Yoshitaka TAKAHASHI
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Keywords: c-myc mRNA coding region determinant-binding protein/insulin-like growth factor II mRNA-binding protein 1 (CRD-BP/IMP-1), human prostate carcinoma PC-3 cells, 8S-lipoxygenase, 15S-lipoxygenase-2
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2009 Volume 73 Issue 8 Pages 1811-1817

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Abstract

8S-Lipoxygenase (8S-LOX) is known as a mouse homolog of human 15S-LOX-2. 15S-LOX-2 was down-regulated in malignant transformation of prostate epithelial cells, and its overexpression caused cell cycle arrest. To determine whether 8S-LOX would have a growth inhibitory effect on prostate carcinoma, we obtained human prostate carcinoma PC-3 cells expressing 8S-LOX or 15S-LOX-2. The growth rate of cells measured by colorimetric assay was reduced by expression of 8S-LOX and 15S-LOX-2. The addition to enzyme-expressing cells of arachidonic acid enhanced the growth suppressive effect, whereas the expression of catalytically inactive mutants did not affect cell growth, suggesting that the effect was product-dependent. DNA microarray and quantitative reverse transcription-PCR analyses revealed that the c-myc mRNA coding region determinant-binding protein/insulin-like growth factor II mRNA-binding protein 1 (CRD-BP/IMP-1), known as an oncofetal protein, was down-regulated in 8S-LOX- and 15S-LOX-2-expressing PC-3 cells. Targeted knockdown of CRD-BP/IMP-1 resulted in inhibition of the DNA synthesis rate of PC-3 cells as measured by bromodeoxyuridine incorporation. We propose that expression of 8S-LOX and 15S-LOX-2 suppresses CRD-BP/IMP-1 expression, resulting in inhibition of human prostate carcinoma PC-3 cell proliferation.

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© 2009 by Japan Society for Bioscience, Biotechnology, and Agrochemistry
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