Reference SummaryWeyant MJ, Cancer Res 2001 Mar 15;61(6):2547-51

Title

Reciprocal expression of ERalpha and ERbeta is associated with estrogen-mediated modulation of intestinal tumorigenesis.

Authors

Weyant MJ; Carothers AM; Mahmoud NN; Bradlow HL; Remotti H; Bilinski RT; Bertagnolli MM

Journal

Cancer Res

Volume

61

Issue

6

Year

2001

Pages

2547-51

Abstract

Menopausal hormone replacement therapy has been widely used to alleviate the symptoms of menopause and to decrease the detrimental effects of ovarian hormone loss on bone density and cardiovascular health. Multiple studies of colorectal cancer epidemiology also support a role for hormone replacement therapy in prevention of colorectal cancer. We studied the effect of ovariectomy and estrogen replacement on tumor formation in C57BL/6J-Min/+ (Min/+) mice, animals that bear a germline mutation in murine Apc. These mice develop multiple intestinal tumors that show loss of wild-type Apc protein. After ovariectomy, intestinal adenomas in Min/+ mice increased by 77% (P = 0.0004). Ovariectomized Min/+ mice that were treated with a replacement dose of 17beta-estradiol had the same number of tumors as Min/+ mice that were neither castrated nor treated with estrogen replacement (P = 0.85). Examination of estrogen receptor (ER) levels in intestinal tissue by immunoblot showed changes in relative expression levels of ERalpha and ERbeta, with highest ERalpha and lowest ERbeta expression in the normal-appearing intestine of Min/+ mice, and lowest ERalpha and highest ERbeta expression in the enterocytes of animals that received 17beta-estradiol. These results suggest that endogenous estrogens protect against Apc-associated tumor formation and that tumor prevention by 17beta-estradiol is associated with an increase in ERbeta and a decrease in ERalpha expression in the target tissue.

Links

J:68469 – MGI References
11289129 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • ovariectomy
Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • 17beta-estradiol (E2)
  • ovariectomy
Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum tumor
  • ovariectomy
Intestine - Small Intestine - Duodenum

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum tumor Intestine - Small Intestine - Duodenum

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum tumor
  • 17beta-estradiol (E2)
  • ovariectomy
Intestine - Small Intestine - Duodenum

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine adenoma
  • ovariectomy
Intestine - Small Intestine

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine adenoma
  • 17beta-estradiol (E2)
  • ovariectomy
Intestine - Small Intestine

observed

C57BL/6J-ApcMin/+ Intestine adenoma
  • ovariectomy
Intestine

observed

C57BL/6J-ApcMin/+ Intestine adenoma Intestine

observed

C57BL/6J-ApcMin/+ Intestine adenoma
  • 17beta-estradiol (E2)
  • ovariectomy
Intestine

observed