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.
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.
Kawakami
Yuki
Y
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Japan.
Kubota
Noriyuki
N
Ekuni
Natsuki
N
Suzuki-Yamamoto
Toshiko
T
Kimoto
Masumi
M
Yamashita
Hiromi
H
Tsuji
Hideaki
H
Yoshimoto
Tanihiro
T
Jisaka
Mitsuo
M
Tanaka
Junko
J
Fujimura
Hirofumi F
HF
Miwa
Yoshihiro
Y
Takahashi
Yoshitaka
Y
D000818:Animals; D001483:Base Sequence; D055162:Biocatalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004318:Doxycycline / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*
C406144:IGF2BP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D008084:Lipoxygenase; D004318:Doxycycline