PML: a tumor suppressor that regulates cell fate in mammary gland
- PMID: 19652541
- DOI: 10.4161/cc.8.17.9462
PML: a tumor suppressor that regulates cell fate in mammary gland
Abstract
The tumor suppressor promyelocytic leukemia protein (PML) is possibly unique in that its tumor suppressive functions may be attributed to both the protein and the conspicuous nuclear bodies (PML-NBs) that PML builds. Untangling the role of either the protein or its domain in cell fate has been a decade long task which has just received new impetus from developmental biologists. PML appears to play a central role in regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Our studies have uncovered an inverse relationship between the activity of certain Stat transcription factors and PML in controlling normal mammary gland development and the regulation of lineage commitment. Genetic loss of Pml delays differentiation of the milk-producing alveolar cells and disrupts ductal development, defects which may result from a skewing of the progenitor population to favor estrogen receptor positive cells (ERalpha). This is of considerable interest as ERalpha cells are non-cycling in normal breast while promiscuous cell cycle entry is a feature of these cells in breast cancer. These data begin to show the cell types and tissues that are most sensitive to PML dose and provide new perspectives for the regulation of mammary gland development and tumorigenesis.
Similar articles
-
PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool.Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4725-30. doi: 10.1073/pnas.0807640106. Epub 2009 Mar 4. Proc Natl Acad Sci U S A. 2009. PMID: 19261859 Free PMC article.
-
E6AP promotes the degradation of the PML tumor suppressor.Cell Death Differ. 2009 Aug;16(8):1156-66. doi: 10.1038/cdd.2009.31. Epub 2009 Mar 27. Cell Death Differ. 2009. PMID: 19325566
-
PML positively regulates interferon gamma signaling.Biochimie. 2011 Mar;93(3):389-98. doi: 10.1016/j.biochi.2010.11.005. Epub 2010 Nov 27. Biochimie. 2011. PMID: 21115099
-
Stemming out of a new PML era?Cell Death Differ. 2009 Aug;16(8):1083-92. doi: 10.1038/cdd.2009.63. Epub 2009 Jun 12. Cell Death Differ. 2009. PMID: 19521423 Review.
-
Cytoplasmic PML: from molecular regulation to biological functions.J Cell Biochem. 2014 May;115(5):812-8. doi: 10.1002/jcb.24727. J Cell Biochem. 2014. PMID: 24288198 Review.
Cited by
-
Promyelocytic leukemia (PML) protein plays important roles in regulating cell adhesion, morphology, proliferation and migration.PLoS One. 2013;8(3):e59477. doi: 10.1371/journal.pone.0059477. Epub 2013 Mar 21. PLoS One. 2013. PMID: 23555679 Free PMC article.
-
Impact of nuclear organization and dynamics on epigenetic regulation in the central nervous system: implications for neurological disease states.Ann N Y Acad Sci. 2010 Sep;1204 Suppl(Suppl):E20-37. doi: 10.1111/j.1749-6632.2010.05718.x. Ann N Y Acad Sci. 2010. PMID: 20840166 Free PMC article. Review.
-
Role of the promyelocytic leukaemia protein in cell death regulation.Cell Death Dis. 2012 Jan 12;3(1):e247. doi: 10.1038/cddis.2011.122. Cell Death Dis. 2012. PMID: 22237204 Free PMC article. Review.
-
Genome Assembly and Evolutionary Analysis of the Mandarin Duck Aix galericulata Reveal Strong Genome Conservation among Ducks.Genome Biol Evol. 2022 May 31;14(6):evac083. doi: 10.1093/gbe/evac083. Genome Biol Evol. 2022. PMID: 35640266 Free PMC article.
-
PML: Regulation and multifaceted function beyond tumor suppression.Cell Biosci. 2018 Jan 25;8:5. doi: 10.1186/s13578-018-0204-8. eCollection 2018. Cell Biosci. 2018. PMID: 29416846 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous
