HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH Cancer Research Clinical Cancer Research Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics Molecular Cancer Research Cancer Prevention Research Cancer Prevention Journals Portal Cancer Reviews Online Annual Meeting Education Book Meeting Abstracts Online		QUICK SEARCH:   [advanced] Author: Keyword(s):

Services Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cho, N. L. Articles by Bertagnolli, M. M. Search for Related Content PubMed Articles by Cho, N. L. Articles by Bertagnolli, M. M.

Proffered Abstract (Oral Presentation): Colorectal Cancer Prevention

Estrogen receptors and ß are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice.

Brigham & Women's Hospital, Boston, MA

Abstract

PR-01

Estrogen replacement therapy in post-menopausal women is associated with a reduction in colorectal cancer (CRC) risk, potentially via interactions between 17ß-estradiol (E₂) and the estrogen receptors and ß (ER/ERß). To study the role of E₂ in intestinal tumor inhibition, we separately crossed C57BL6-J/Min/+ (Min/+) mice with Er^+/- and Erß^+/- mice to generate Er-deficient Min/+ progeny. We found an increased incidence of visible colon tumors and dysplastic microadenomas in Er-deficient Min/+ relative to Er^+/+Min/+ controls. Small intestinal tumor numbers were unaffected. Invasive carcinomas were found only in Er^+/-Min/+ mice, suggesting that Er plays additional non-cell autonomous roles that limit tumor progression. Histological analyses of Er-deficient Min/+ colons, as well as colons from ovariectomized Min/+ (OvxMin/+) and E₂-treated OvxMin/+ (OvxMin/+ +E₂) revealed significant differences in crypt architecture, enterocyte proliferation, and goblet cell differentiation relative to Min/+ and Er^+/+Apc^+/+ (WT) controls. The expression of Er and Erß was regionally compartmentalized along the colonic crypt axis, suggesting functional antagonism. Our results indicate that Er and Erß are inhibitory modifiers of Apc-dependent colon tumorigenesis. As a result, loss of E₂ and ER signaling in post-menopausal women may contribute to CRC development.