Advanced

Identification of differentially expressed genes after PPM1D silencing in breast cancer.

Pärssinen, Jenita; Alarmo, Emma-Leena; Khan, Sofia; Karhu, Ritva; Vihinen, Mauno LU and Kallioniemi, Anne (2008) In Cancer Letters 259(1). p.61-70
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
RNA, Phosphoprotein Phosphatases: metabolism, Phosphoprotein Phosphatases: genetics, Gene Expression Profiling: methods, Breast Neoplasms: genetics, Breast Neoplasms: metabolism, Small Interfering: metabolism, Signal Transduction: genetics
in
Cancer Letters
volume
259
issue
1
pages
61 - 70
publisher
Elsevier
external identifiers
  • pmid:17977650
  • scopus:36849058152
ISSN
1872-7980
DOI
10.1016/j.canlet.2007.09.019
language
English
LU publication?
no
id
a9ab563e-7162-407a-8bf3-16ef4dfd6a01 (old id 3635208)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/17977650?dopt=Abstract
date added to LUP
2013-06-12 16:28:05
date last changed
2017-03-19 04:22:30
@article{a9ab563e-7162-407a-8bf3-16ef4dfd6a01,
  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.},
  author       = {Pärssinen, Jenita and Alarmo, Emma-Leena and Khan, Sofia and Karhu, Ritva and Vihinen, Mauno and Kallioniemi, Anne},
  issn         = {1872-7980},
  keyword      = {RNA,Phosphoprotein Phosphatases: metabolism,Phosphoprotein Phosphatases: genetics,Gene Expression Profiling: methods,Breast Neoplasms: genetics,Breast Neoplasms: metabolism,Small Interfering: metabolism,Signal Transduction: genetics},
  language     = {eng},
  number       = {1},
  pages        = {61--70},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Identification of differentially expressed genes after PPM1D silencing in breast cancer.},
  url          = {http://dx.doi.org/10.1016/j.canlet.2007.09.019},
  volume       = {259},
  year         = {2008},
}