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Publication
Expression of MYCN in Multipotent Sympathoadrenal Progenitors Induces
Proliferation and Neural Differentiation, but Is Not Sufficient for
Tumorigenesis.
Authors Mobley BC, Kwon M, Kraemer BR, Hickman FE, Qiao J, Chung DH, Carter BD
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal PLoS ONE
Year 2015
Date Published
Volume : Pages 10 : e0133897
PubMed Reference 26222553
Abstract Neuroblastoma is a pediatric malignancy of the sympathetic ganglia and adrenal
glands, hypothesized to originate from progenitors of the developing sympathetic
nervous system. Amplification of the MYCN oncogene is a genetic marker of risk
in this disease. Understanding the impact of oncogene expression on
sympathoadrenal progenitor development may improve our knowledge of
neuroblastoma initiation and progression. We isolated sympathoadrenal progenitor
cells from the postnatal murine adrenal gland by sphere culture and found them
to be multipotent, generating differentiated colonies of neurons, Schwann cells,
and myofibroblasts. MYCN overexpression in spheres promoted commitment to the
neural lineage, evidenced by an increased frequency of neuron-containing
colonies. MYCN promoted proliferation of both sympathoadrenal progenitor spheres
and differentiated neurons derived from these spheres, but there was also an
increase in apoptosis. The proliferation, apoptosis, and neural lineage
commitment induced by MYCN are tumor-like characteristics and thereby support
the hypothesis that multipotent adrenal medullary progenitor cells are cells of
origin for neuroblastoma. We find, however, that MYCN overexpression is not
sufficient for these cells to form tumors in nude mice, suggesting that
additional transforming mutations are necessary for tumorigenesis.




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