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.

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Bioscience, biotechnology, and biochemistry

دوره 73 8  شماره 

صفحات  -

تاریخ انتشار 2009