O'Brien, 1997  Title: Ornithine decarboxylase overexpression
is a sufficient condition for tumor promotion in mouse skin.
Authors: O'Brien TG, Megosh LC, Gilliard G,
Soler AP
Journal: Cancer Res 1997 Jul 1;57(13):2630-7
PMID: 9205069, UI: 97349065
Affiliated institution: The Lankenau
Medical Research Center, Wynnewood, Pennsylvania 19096, USA.
Cited in:
In multistage tumorigenesis models, ornithine decarboxylase (ODC)
is usually dysregulated at some point during tumor promotion,
an early stage of carcinogenesis. To address the question whether
constitutive overexpression of ODC would be a sufficient condition
for tumor promotion, mice with high levels of ODC expression targeted
to epidermal keratinocytes were used in skin tumorigenesis experiments.
Transgenic mice with ODC targeted to hair follicle keratinocytes
were much more sensitive than littermate controls to initiation
with a single low dose of carcinogen; in fact, such mice no longer
required treatment with tumor promoters for tumors to develop.
Targeting ODC overexpression to both interfollicular and follicular
keratinocytes did not further enhance tumor yield. Our results
suggest that most, if not all, target cells for chemical carcinogens
in the skin reside in hair follicles, and ODC overexpression is
sufficient to activate such cells to expand clonally to form epidermal
tumors.
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