Dietary components modify gene expression: implications for carcinogenesis.
Mouse genetic models that probe important pathways in intestinal cell maturation, such as cell-cycle regulation, apoptosis, and, especially, lineage specific differentiation, have provided profound insight into the underlying mechanisms of intestinal tumor formation and progression. However, a wealth of epidemiological and experimental data indicates that environment, especially the diet, is a principal determinant of relative risk for tumor development. We have demonstrated that even in mouse models in which tumor incidence is strongly initiated by genetic manipulation of genes, such as Apc, p21(WAF1/cip1), and p27(Kip1), a Western-style diet that is high in fat and low in calcium and vitamin D can dramatically increase and accelerate tumor formation. Moreover, experiments show that modulation of calcium and vitamin D levels can substantially influence tumor formation in both the mouse genetic models, as well as in a new dietary model that appears to mimic the development of sporadic colon cancer. Finally, analysis of gene expression profiles provides important insights into how diets may alter metabolic profiles and regulatory pathways that influence probability of tumor formation in the histologically and physiologically normal intestinal mucosa.
Yang
Kan
K
Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, NY 10467, USA.
Yang
Wancai
W
Mariadason
John
J
Velcich
Anna
A
Lipkin
Martin
M
Augenlicht
Leonard
L
D000818:Animals; D002136:Calcium, Dietary / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D016259:Genes, myc / Q000502:physiology; D007413:Intestinal Mucosa / Q000473:pathology; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D023421:Models, Animal; D014807:Vitamin D / Q000008:administration & dosage
D002136:Calcium, Dietary; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004041:Dietary Fats; D014807:Vitamin D