Control of Colon Cancer Development and Progression by Selected Estrogen Receptor Modulators

Valentina Martineti; Sandra Silvestri; Francesco Tonelli; Maria Luisa Brandi

Disclosures

Expert Rev Endocrinol Metab. 2008;3(4):503-511. 

In This Article

Abstract and Introduction

Abstract

Estrogens behave as protective agents on the development of colorectal cancer, and hormonal-replacement therapy is associated with an increased survival rate in women with this disease, indicating that estrogenic therapy correlates with a better prognosis. The protective effect of estrogens on Fcolorectal cancer development and progression is presumably related to the expression of estrogen receptors in colon mucosa, with the estrogen receptor-β isoform being the predominant one. This observation suggests that estrogen receptor-β could have an inhibitory effect on colorectal cancer cell proliferation and a regulatory effect on colonic mucosa cell growth, opening the discussion on a pharmacologic approach to colorectal cancer prevention and therapy based on estrogenic compounds.

Introduction

Colorectal cancer (CRC) is the second most common neoplasm in both genders and its incidence has been rising during the last decades both in industrialized and developing countries. Estrogens appear to act as protective agents on the development of CRC, and hormonal-replacement therapy (HRT) after menopause reduces colon cancer risk to 0.55-0.65. HRT is also associated with an increased survival rate in women with CRC, indicating that estrogen uptake correlates with better prognosis of tumors. Reduction in rectal cancer risk by estrogens is lower: only 0.81 in postmenopausal women under HRT.

The protective effect of estrogens on CRC development and progression is presumably related to the documented expression of estrogen receptors (ERs) in colon mucosa, with the ERβ isoform being expressed at a higher level with respect to ERa. Moreover, a significant decline in ERβ expression levels has been observed along the transition from normal mucosa to neoplastic lesions. This observation suggests that ERβ could have an inhibitory effect on CRC cell proliferation and a regulatory effect on colonic mucosa cell growth. Indeed, the inhibitory effect of ERβ on cell proliferation through regulation of cell cycle progression has been demonstrated in both In vitro and in vivo studies, opening the discussion on a pharmacologic approach to CRC prevention and therapy based on estrogenic molecules.

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