Polyamine metabolism and tumorigenesis in the Apc(Min/+) mouse.
While polyamine homoeostasis is clearly important in maintenance of normal cell function, the roles of these cations, as well as the enzymes that regulate their metabolism, in the neoplastic process are not clear. In particular, the polyamine catabolic enzyme SSAT (spermidine/spermine N(1)-acetyltransferase) seems to have different roles in tumorigenesis, depending upon the particular system being analysed. In attempts to clarify the function of SSAT in tumour development, we have utilized the Apc(Min/+) mouse, which carries a mutant allele of the Apc (adenomatous polyposis coli) gene, rendering it susceptible to the formation of multiple adenomas in the small intestine and colon. Using genetically engineered animals (i.e. transgenic and knockout mice), we have shown that SSAT acts as a tumour promoter in the Apc(Min/+) model. Modulation of tumorigenesis is not associated with changes in tissue levels of either spermidine or spermine. These findings, along with those made in other animal models of cancer, have prompted us to propose that metabolic flux through the polyamine biosynthetic and catabolic pathways, and the consequent changes in levels of various metabolites within the cell (i.e. the metabolome), is critical to tumour development. The metabolic flux model represents a novel way of thinking about the role of polyamines in cell physiology and the neoplastic process.
Berger
F G
FG
Department of Biological Sciences and Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA. berger@sc.edu
Kramer
D L
DL
Porter
C W
CW
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D017491:Genes, APC; D005818:Genetic Engineering; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D009955:Ornithine Decarboxylase; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase