Widespread hyperplasia induced by transgenic TGFalpha in ApcMin mice is associated with only regional effects on tumorigenesis.
Using a mouse predisposed to neoplasia by a germ line mutation in Apc (Apc(Min)), we tested whether induced hyperplasia is sufficient to increase intestinal tumor multiplicity or size in the intestine. We found that hyperplasia in the jejunum correlated with a significant increase in tumor multiplicity. However, tumor multiplicity was unchanged in the hyperplastic colon. This result indicates that even an intestine predisposed to neoplasia can, in certain regions including the colon, accommodate net increased cell growth without developing more neoplasms. Where hyperplasia correlated with increased tumor multiplicity, it did not increase the size or net growth of established tumors. This result suggests that the event linking hyperplasia and neoplasia in the jejunum is tumor establishment. Two novel observations arose in our study: the multiple intestinal neoplasia (Min) mutation partially suppressed both mitosis and transforming growth factor alpha-induced hyperplasia throughout the intestine; and zinc treatment alone increased tumor multiplicity in the duodenum of Min mice.
Bilger
Andrea
A
Department of Oncology, McArdle Laboratory for Cancer Research, University ofWisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Sullivan
Ruth
R
Prunuske
Amy J
AJ
Clipson
Linda
L
Drinkwater
Norman R
NR
Dove
William F
WF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology*; D004379:Duodenal Neoplasms / Q000209:etiology / Q000473:pathology*; D005038:Ethylnitrosourea; D005260:Female; D017491:Genes, APC / Q000502:physiology*; D006965:Hyperplasia / Q000139:chemically induced* / Q000473:pathology; D007078:Ileal Neoplasms / Q000209:etiology / Q000473:pathology*; D007580:Jejunal Neoplasms / Q000209:etiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008938:Mitosis; D009154:Mutation; D016211:Transforming Growth Factor alpha / Q000502:physiology*; D019076:Transgenes / Q000502:physiology; D015032:Zinc / Q000008:administration & dosage
D016211:Transforming Growth Factor alpha; D015032:Zinc; D005038:Ethylnitrosourea