Journal
CARCINOGENESIS
Volume 32, Issue 11, Pages 1675-1683Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgr188
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Funding
- DFG [716/10-3, GK1427]
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Epidemiological data indicate that intake of estrogens and isoflavones may be beneficial for the prevention of colorectal cancer (CRC). Based on this data, the aim of the study was to investigate estrogen receptor (ER) subtype-specific effects on intestinal homeostasis. Ovariectomized (OVX) female Wistar rats were either treated with 17 beta-estradiol (4 mu g/kg body wt/day) (E2), an ER alpha-specific agonist (ALPHA) (10 mu g/kg body wt/day), an ER beta-specific agonist (BETA) (100 mu g/kg body wt/day) or genistein (GEN) (10 mg/kg body wt/day) for three weeks. Vehicle-treated OVX and SHAM animals and those cotreated with BETA and the pure antiestrogen Fulvestrant (ICI 182780) (100 mu g/kg body wt/day and 3 mg/kg body wt/day) served as controls. GEN and BETA treatment but not E2 and ALPHA administration reduced proliferation in ileal and colonic mucosa cells. The rate of apoptosis in the small intestine and colon was increased by treatment with BETA and GEN, but not by E2. BETA induced antiproliferative and proapoptotic activity also in SHAM animals. The effects were antagonized by the pure antiestrogen Fulvestrant. Polymerase chain reaction gene array analysis revealed that BETA resulted in the downregulation of the oncogene transformation-related protein 63 (p63). Our data indicate that activation of the ER beta by specific ER beta agonists and GEN induces antiproliferative and proapoptotic effects in the intestinal tract. This observation can be taken as an indication that intake of GEN and specific ER beta agonists may protect the ileal and colonic epithelium from tumor development via modulation of tissue homeostasis.
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