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Intestinal tumors adapt to excess dietary iron by altering expression of lipocalin‐2 and divalent metal ion transporter
Author(s) -
Swain James,
Li Chunbiao,
Leahy Patrick
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.694.3
Subject(s) - dmt1 , ferrous , chemistry , transporter , lipocalin , gene expression , divalent metal , metal , metabolism , gene , biochemistry , microbiology and biotechnology , biology , organic chemistry
To determine the effect of excess dietary iron on gene expression of intestinal tumors in an animal model of human familial adenomatous polyposis, male C57BL/6J Apc Min/+ mice were fed adequate and excess amounts of iron (ferrous sulfate: 45 vs. 450 mg iron/kg AIN‐93M[M] diet). After 10 wk, mice were sacrificed and intestines removed. Tumors and adjacent non‐tumor tissue were excised and RNA isolated for micro‐array analysis (n=3/group; Mouse Genome 430A 2.0 arrays; Affymetrix) and RT‐PCR. Pathway mapping was performed to reveal gene networks (Pathway Studio 4.0, Ariadne Genomics, Inc.; Gene Spring , Agilent, Inc.; Searcher, Lucidyx). Bayesian ANOVA was used for micro‐arrays. Data show there was an approximate 3‐fold increase in the expression of lipocalin‐2 and a 9‐fold decrease in expression of the proton‐coupled divalent metal ion transporter (DMT; solute carrier family 11, member 2) with excess iron. Findings reveal that intestinal tumors adapt to excess dietary iron by increasing expression of lipocalin‐2, possibly to assist in sequestering increased cytosolic iron, and decreasing expression of DMT, thereby limiting iron absorption. Supported in part by grants IRG‐91‐022 from ACS (to JS) and P30CA43703 from NIH. Ferrous sulfate provided by Crown Technologies, Inc.