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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Pärssinen J,Alarmo EL,Khan S,Karhu R,Vihinen M,Kallioniemi Adoi
10.1016/j.canlet.2007.09.019subject
Has Abstractpub_date
2008-01-18 00:00:00pages
61-70issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(07)00455-7journal_volume
259pub_type
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