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

Biosci Biotechnol Biochem. 2009 Aug;73(8):1811-7. doi: 10.1271/bbb.90185. Epub 2009 Aug 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Biocatalysis
  • Cell Line, Tumor
  • Cell Proliferation
  • Doxycycline / pharmacology
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Knockdown Techniques
  • Genes, myc / genetics*
  • Humans
  • Lipoxygenase / metabolism*
  • Male
  • Mice
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*

Substances

  • IGF2BP1 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Lipoxygenase
  • Doxycycline