Downregulation of delta-aminolevulinate dehydratase is associated with poor prognosis in patients with breast cancer

Cancer Sci. 2017 Apr;108(4):604-611. doi: 10.1111/cas.13180. Epub 2017 Apr 12.

Abstract

Delta-aminolevulinate dehydratase (ALAD) catalyzes the second step in the biosynthesis of heme and is also an endogenous inhibitor of the 26S proteasome. The role of ALAD in breast cancer progression is still unclear. In this study, we found that the expression of ALAD was downregulated in breast cancer tissues compared with adjacent normal breast tissues. Enhanced ALAD expression was associated with a favorable outcome in patients with breast cancer. Overexpression of ALAD suppresses breast cancer cell proliferation and invasion and inhibits the epithelial-mesenchymal transition phenotype. Furthermore, we found that ALAD regulates transforming growth factor-β-mediated breast cancer progression. This finding suggests that ALAD might be a potential biomarker for breast cancer that suppresses breast cancer progression by regulating transforming growth factor-β-mediated epithelial-mesenchymal transition.

Keywords: ALAD; TGF-β; breast cancer; epithelial-mesenchymal transition; prognostic factor.

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation*
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Microscopy, Fluorescence
  • Porphobilinogen Synthase / genetics*
  • Porphobilinogen Synthase / metabolism
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • Porphobilinogen Synthase

Associated data

  • GENBANK/GSE11121
  • GENBANK/GSE12093
  • GENBANK/GSE2034
  • GENBANK/GSE2603
  • GENBANK/GSE5327
  • GENBANK/GSE6532
  • GENBANK/GSE7390