Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: a mechanism of proliferation and apoptosis in cancer

Mol Med Rep. 2012 Nov;6(5):983-8. doi: 10.3892/mmr.2012.1067. Epub 2012 Sep 5.

Abstract

Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates embryological pancreas development and insulin expression in adult islets. The current study investigated the expression profile and potential role of PDX-1 in breast cancer. Immunohistochemistry was performed to determine the expression pattern of PDX-1 in breast cancer and adjacent benign breast tissues. In addition, cell proliferation and the cell cycle were evaluated following the transient inhibition of PDX-1 with antisense oligonucleotides in MCF-7 human breast cancer cells. Real-time PCR and western blotting were conducted to investigate the correlation between PDX-1, P53, Ki-67, Caspase 3 and Caspase 8. These experiments demonstrated that PDX-1 was downregulated in human breast cancer tissue compared with adjacent normal breast tissue. Knockdown of PDX-1 expression in vitro in MCF-7 breast cancer cells promoted cell proliferation and disrupted the cell cycle, as demonstrated by the overexpression of P53 and Ki-67 at the mRNA and protein levels. In conclusion, the current study shows that PDX-1 regulates cell proliferation and the cell cycle in human breast cancer cells by altering the expression of the cell cycle-related genes, P53 and Ki-67. These data suggest that PDX-1 is a putative tumor suppressor in breast cancer.

Keywords: breast cancer; PDX-1; tumur suppressor gene.

MeSH terms

  • Apoptosis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • MCF-7 Cells
  • Middle Aged
  • Neoplasm Staging
  • Oligonucleotides, Antisense / metabolism
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Homeodomain Proteins
  • Ki-67 Antigen
  • Oligonucleotides, Antisense
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • pancreatic and duodenal homeobox 1 protein
  • Caspase 3
  • Caspase 8