Journal Article

Dietary-induced ERβ upregulation counteracts intestinal neoplasia development in intact male Apc<sup>Min/+</sup> mice

Michele Barone, Sabina Tanzi, Katia Lofano, Maria Principia Scavo, Maria Pricci, Lucia Demarinis, Samanta Papagni, Raffaella Guido, Eugenio Maiorano, Giuseppe Ingravallo, Maria Cristina Comelli, Antonio Francavilla and Alfredo Di Leo

in Carcinogenesis

Volume 31, issue 2, pages 269-274
Published in print February 2010 | ISSN: 0143-3334
Published online November 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp275
Dietary-induced ERβ upregulation counteracts intestinal neoplasia development in intact male ApcMin/+ mice

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Most sporadic colorectal cancers (CRCs) develop through the adenoma–carcinoma sequence pathway and are initiated by adenomatous polyposis coli (APC) gene mutations. Estrogen receptor beta (ERβ) is recognized to progressively reduce its expression in adenomatous and carcinomatous tissues in humans. Moreover, ERβ deficiency enhances small intestinal tumorigenesis in rodents. In the ApcMin/+ mouse model, we evaluated intestinal polyp development and ERβ expression plus other biological parameters influencing tumor growth (epithelial cell proliferation, apoptosis and migration) following the addition of a combination of the ERβ-selective agonist silymarin (SIL) and/or lignin (LIG) to a high-fat/low-fiber diet. Forty-five ApcMin/+ mice were divided in four groups: animals fed on the tumorigenic high-fat/low-fiber diet, the tumorigenic diet supplemented with SIL (0.02%) or purified LIG (6.24%) or SIL (0.005%) + LIG (6.24%). In these animals, we assessed polyp number and volume and their degree of dysplasia together with ERβ messenger RNA (mRNA) and protein levels and epithelial cell proliferation, migration and apoptosis. The latter group of parameters was evaluated in normal and adenomatous mucosa and the results compared with those found in wild-type (WT) mice fed on the control diet. The addition of SIL or LIG to the diet and even more the specific combination of the two significantly counteracted intestinal tumorigenesis and increased ERβ mRNA and protein levels. Cell proliferation and apoptosis were rebalanced and cell migration accelerated, restoring values similar to those observed in WT animals. Our results further support a protective effect of ERβ in CRC suggesting the use of the combination of SIL-LIG as a potential approach against CRC development.

Journal Article.  5359 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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