Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis.

The Journal of Biological Chemistry
Myung-Jeom RyuJing Zhang

Abstract

Previous studies suggest that up-regulation of Ras signaling in neurons promotes gliosis and astrocytoma formation in a cell nonautonomous manner. However, the underlying mechanisms remain unknown. To address this question, we generated compound mice (LSL Kras G12D/+;CamKII-Cre) that express oncogenic Kras from its endogenous locus in postmitotic neurons after birth. These mice developed progressive gliosis, which is associated with hyperactivation of Ras signaling pathways. Microarray analysis identified S100A8 and S100A9 as two secreted molecules that are significantly overexpressed in mutant cortices. In contrast to their usual predominant expression in myeloid cells, we found that overexpression of S100A8 and S100A9 in the mutant cortex is primarily in neurons. This neuronal expression pattern is associated with increased infiltration of microglia in mutant cortex. Moreover, purified S100A8-S100A9 but not S100A8 or S100A9 alone promotes growth of primary astrocytes in vitro through both TLR4 and receptor of advanced glycation end product receptors. In summary, our results identify overexpression of S100A8-S100A9 in neurons as an early step in oncogenic Kras-induced gliosis. These molecules expressed in nonhematopoietic cell...Continue Reading

References

Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·O StewardE Lothman
Jun 1, 1980·The Journal of Cell Biology·K D McCarthy, J de Vellis
Jul 1, 1995·Journal of Neuropathology and Experimental Neurology·M L NordlundN Ratner
Jan 7, 1998·Trends in Neurosciences·J L RidetF H Gage
Aug 10, 2000·Neuropathology and Applied Neurobiology·D H GutmannA Perry
Nov 18, 2000·The Journal of Biological Chemistry·K K HiattD W Clapp
Jun 22, 2002·Molecular and Cellular Biology·Michaela Livia BajenaruDavid H Gutmann
Mar 18, 2003·Molecular and Cellular Biology·Josie A R HobbsNancy Hogg
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johannes RothClemens Sorg
Dec 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Benjamin S BraunKevin M Shannon
Jun 17, 2005·Journal of Neuroscience Research·Jyoti J WattersBehnam Badie
Jul 19, 2006·Biochemical Pharmacology·Christoffer GebhardtJochen Hess
May 10, 2007·Nature Protocols·Astrid E CardonaRichard M Ransohoff
Aug 23, 2007·Neuropediatrics·W G JanzarikH Omran
Oct 28, 2008·Journal of Child Neurology·David H Gutmann
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Aug 12, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Julia NémethJochen Hess
Sep 8, 2009·BMC Bioinformatics·Aaron L VollrathChristopher A Bradfield
Oct 20, 2009·European Journal of Pharmacology·Saeid GhavamiClaus Kerkhoff
Jan 7, 2010·The Journal of Clinical Investigation·José M González-NavajasEyal Raz
Apr 22, 2010·Cancer Research·Daniela S BassèresAlbert S Baldwin
Jan 14, 2011·Molecular Cancer Research : MCR·Mie IchikawaGeetha Srikrishna

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Citations

Nov 19, 2013·Acta Neuropathologica·Chao WangLudmilla A Morozova-Roche
Mar 26, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuguang ZhaoShuang Wang
Mar 24, 2018·International Journal of Oncology·Zhanhui DuShangming Liu

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