Identification of differentially expressed genes after PPM1D silencing in breast cancer

Cancer Lett. 2008 Jan 18;259(1):61-70. doi: 10.1016/j.canlet.2007.09.019. Epub 2007 Oct 30.

Abstract

Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent 1 delta) has been observed in various cancer cell lines and primary tumors and has also been associated with cancers of poor prognosis. In addition to the negative feedback regulation of p38-p53 signaling, PPM1D inhibits other tumor suppressor activities and is involved in the control of DNA damage and repair pathways. To elucidate the functional significance of PPM1D in breast cancer, we employed RNA interference to downregulate PPM1D expression in BT-474, MCF7, and ZR-75-1 breast cancer cell lines and then investigated the effects of PPM1D silencing on global gene expression patterns and signaling pathways using oligonucleotide microarrays. We identified 1798 differentially expressed (at least a two-fold change) gene elements with functions related to key cellular processes, such as regulation of cell cycle, assembly of various intracellular structures and components, and regulation of signaling pathways and metabolic cascades. For instance, genes involved in apoptosis (NR4A1, RAB25, PLK1), formation of nucleosome structure (HIST1H2AC, HIST1H2BF, HIST1H2BO, HIST1H1D), and hormone related activities (NR4A1, ESR1, STC1) were among the differentially expressed genes. Overall, our findings suggest that PPM1D contributes to breast cancer associated phenotypic characteristics by directly or indirectly affecting several important cellular signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cluster Analysis
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Protein Phosphatase 2C
  • RNA Interference*
  • RNA, Small Interfering / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Transfection

Substances

  • RNA, Small Interfering
  • PPM1D protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2C