Abstract
Hormones have become a useful therapeutic aspect of clinical endocrinology but how to use them to optimize the health benefits and avoid adverse effects is a major challenge. Estrogen is an indispensable hormone for proper biological functioning but is also implicated with the pathology of both the reproductive and non-reproductive tissues. Abnormal estrogen receptor signaling may increase the risk of development of a variety of diseases including colorectal cancer (CRC). Estrogen receptor beta (ERβ) is the predominant subtype in the colonic epithelium and confers the anti-tumor effect through various mechanisms. Many investigators have embarked on the search for the biological mechanisms by which estrogen and estrogen-like compounds may influence the pathogenesis of CRC. This review explores the recent findings on the therapeutic role of ERβ in the colonic epithelium as a prospective candidate for targeted endocrine therapy in CRC.
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References
World Health Organization (2018) Global health observatory. World Health Organization, Geneva
Gulbake A et al (2016) Insight to drug delivery aspects for colorectal cancer. World J Gastroenterol 22(2):582–599
Stevanato Filho PR et al (2017) Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer. BMC Cancer 17(1):754
Fitzmaurice C et al (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015 a systematic analysis for the global burden of disease study. JAMA Oncol 3(4):524–548
Barzi A et al (2013) Molecular pathways: estrogen pathway in colorectal cancer. Clin Cancer Res 19(21):5842–5848
Yang X et al (2017) Estrogen and estrogen receptors in the modulation of gastrointestinal epithelial secretion. Oncotarget 8(57):97683–97692
Saint-Criq V et al (2012) Estrogen regulation of epithelial ion transport: implications in health and disease. Steroids 77(10):918–923
Song CH et al (2019) Effects of 17beta-estradiol on colorectal cancer development after azoxymethane/dextran sulfate sodium treatment of ovariectomized mice. Biochem Pharmacol 164:139–151
Heijmans J et al (2014) Oestrogens promote tumorigenesis in a mouse model for colitis-associated cancer. Gut 63(2):310–316
Saleiro D et al (2012) Estrogen receptor-beta protects against colitis-associated neoplasia in mice. Int J Cancer 131(11):2553–2561
Giroux V et al (2008) Estrogen receptor beta deficiency enhances small intestinal tumorigenesis in ApcMin/+ mice. Int J Cancer 123(2):303–311
Armstrong CM et al (2013) A novel shift in estrogen receptor expression occurs as estradiol suppresses inflammation-associated colon tumor formation. Endocr Relat Cancer 20(4):515–525
Murphy N et al (2017) Reproductive and menstrual factors and colorectal cancer incidence in the women's health initiative observational study. Br J Cancer 116(1):117–125
Rudolph A et al (2013) Colorectal cancer risk associated with hormone use varies by expression of estrogen receptor-beta. Cancer Res 73(11):3306–3315
Botteri E et al (2017) Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway. BMJ Open 7(11):e017639
Cobin RH, Goodman NF (2017) American association of clinical endocrinologists and American college of endocrinology position statement on Menopause-2017 update. Endocr Pract 23(7):869–880
Greene GL et al (1986) Sequence and expression of human estrogen receptor complementary DNA. Science 231(4742):1150–1154
Caiazza F et al (2015) Estrogen receptors and their implications in colorectal carcinogenesis. Front Oncol 5:19
Jacenik D et al (2019) G protein-coupled estrogen receptor in colon function, immune regulation and carcinogenesis. World J Gastroenterol 25(30):4092–4104
Acconcia F et al (2005) Survival versus apoptotic 17beta-estradiol effect: role of ER alpha and ER beta activated non-genomic signaling. J Cell Physiol 203(1):193–201
Galluzzo P et al (2007) Role of ERbeta palmitoylation in the inhibition of human colon cancer cell proliferation. Endocr Relat Cancer 14(1):153–167
Barone M, Di Leo AJJGSGT (2013) Estrogen receptor beta in colorectal cancer prevention: do we have conclusive proof. Front Oncol 4(201):2
Huang B et al (2014) Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer. J Genet Syndr Gene Ther 111(5):1933–1938
Looijer-van Langen M et al (2011) Estrogen receptor-β signaling modulates epithelial barrier function. Am J Physiol Gastrointest Liver Physiol 300(4):G621–G626
Pierdominici M et al (2015) Linking estrogen receptor β expression with inflammatory bowel disease activity. Oncotarget 6(38):40443–40451
Rudolph A et al (2012) Expression of oestrogen receptor beta and prognosis of colorectal cancer. Br J Cancer 107(5):831–839
Sareddy GR, Vadlamudi RK (2015) Cancer therapy using natural ligands that target estrogen receptor beta. Chin J Nat Med 13(11):801–807
Xie L-Q, Yu J-P, Luo H-SJWJOG (2004) Expression of estrogen receptor β in human colorectal cancer. World J Gastroenterol 10(2):214
Wada-Hiraike O et al (2006) Role of estrogen receptor β in colonic epithelium. Proc Natl Acad Sci 103(8):2959–2964
Edvardsson K et al (2011) Estrogen receptor beta induces antiinflammatory and antitumorigenic networks in colon cancer cells. Mol Endocrinol 25(6):969–979
Williams C et al (2016) Estrogen receptor beta as target for colorectal cancer prevention. Cancer Lett 372(1):48–56
Wei Y et al (2019) Estrogen receptor beta (ERβ) mediated-CyclinD1 degradation via autophagy plays an anti-proliferation role in colon cells. Int J Biol Sci 15(5):942
Hartman J et al (2009) Tumor repressive functions of estrogen receptor beta in SW480 colon cancer cells. Cancer Res 69(15):6100–6106
Perez-Ruiz E et al (2018) Expression and prognostic value of oestrogen receptor beta in colorectal cancer. Pathol Oncol Res 24(4):871–879
Nelson AW et al (2017) Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity. Mol Cell Endocrinol 440:138–150
Andersson S et al (2017) Insufficient antibody validation challenges oestrogen receptor beta research. Nat Commun 8:15840–15840
Iacopetta BJIJOC (2002) Are there two sides to colorectal cancer? Int J Cancer 101(5):403–408
Papaxoinis K et al (2010) Subsite-specific differences of estrogen receptor beta expression in the normal colonic epithelium: implications for carcinogenesis and colorectal cancer epidemiology. Eur J Gastroenterol Hepatol 22(5):614–619
Koo JH, Leong RWJJOG (2010) Sex differences in epidemiological, clinical and pathological characteristics of colorectal cancer. J Gastroenterol Hepatol 25(1):33–42
Jassam N et al (2005) Loss of expression of oestrogen receptor beta in colon cancer and its association with Dukes' staging. Oncol Rep 14(1):17–21
Yamauchi M et al (2012) Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 61(6):847–854
Rosty C et al (2013) PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival. PLoS ONE 8(6):e65479
Parmeggiani D et al (2011) Additional prognostic factors in right colon cancer staging. Updates Surg 63(3):155–161
Bolli A et al (2010) Bisphenol A impairs estradiol-induced protective effects against DLD-1 colon cancer cell growth. IUBMB Life 62(9):684–687
Qi W et al (2011) Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer 11:219
Schleipen B et al (2011) ERbeta-specific agonists and genistein inhibit proliferation and induce apoptosis in the large and small intestine. Carcinogenesis 32(11):1675–1683
Guo JY et al (2004) Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild-type mice from carcinogen-induced colon cancer. J Nutr 134(1):179–182
Zou Y et al (2019) Isoflavone and its metabolite equol inhibit development of azoxymethane-induced colorectal tumors and modulate proliferation of colon carcinoma cells. Int J Clin Exp Med 12(1):461–469
Menon R et al (2013) Diet complexity and estrogen receptor beta status affect the composition of the murine intestinal microbiota. Appl Environ Microbiol 79(18):5763–5773
Pampaloni B et al (2013) Phytoestrogens and colon cancer. In: Soybean—bio-active compounds
Eisenbrand G (2007) Isoflavones as phytoestrogens in food supplements and dietary foods for special medical purposes. Opinion of the senate commission on food safety (SKLM) of the German Research Foundation (DFG)-(shortened version). Mol Nutr Food Res 51(10):1305–1312
Yan L, Spitznagel EL, Bosland MC (2010) Soy consumption and colorectal cancer risk in humans: a meta-analysis. Cancer Epidemiol Biomark Prev 19(1):148–158
Funding
The current study was supported by grants from the National Natural Science Foundation of China (Grant No. 31672520), the Fundamental Research Funds for the Central Universities (Grant No. KJQN201709), the National Natural Science Foundation of China (Grant No. 31602027), the National Natural Science Foundation of China (Grant No. 31372403), Jiangsu Natural Science Foundation of China (Grant No. BK20160732), China Postdoctoral Science Foundation (2016M591860), the Priority Academic Program Development of Jiangsu Higher Education Institutions, Graduate Research and Innovation Projects in Jiangsu Province.
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Maingi, J.W., Tang, S., Liu, S. et al. Targeting estrogen receptors in colorectal cancer. Mol Biol Rep 47, 4087–4091 (2020). https://doi.org/10.1007/s11033-020-05414-6
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DOI: https://doi.org/10.1007/s11033-020-05414-6