Regulation of Cell Growth by Estrogen Signaling and Potential Targets in Thyroid Cancer

Abstract

Thyroid cancer occurs three times more frequently in females than in males, and in females the incidence decreases after menopause. This gender difference suggests that the growth and progression of thyroid cancer may be influenced by female sex hormones, particularly estrogens. Experimental data have clearly demonstrated that estrogens can influence cancer cell growth. The action of estrogens on target sites is mediated through related but distinct estrogen receptors, designated estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta), both of which are known to be expressed in thyroid cancer cells. The proliferation of thyroid cancer cells is promoted by an ERalpha agonist, whereas the proliferation is reduced by the enhanced expression of ERbeta or by an ERbeta agonist. When ERbeta is down-regulated, the proliferation of thyroid cells is significantly increased. Studies have shown that the expression of ERalpha in thyroid cancer cells is increased while the expression of ERbeta is either very low or absent. In conclusion, it appears that estrogens have opposite effects on the growth of thyroid cancer cells, depending on the balance between ERalpha and ERbeta in the cells. The modulation of ERalpha and ERbeta and the intervention of their pathways may open up new potential targets for the treatment of thyroid cancer.

Expression of the estrogen receptor α, progesterone receptor and epidermal growth factor receptor in papillary thyroid carcinoma tissues

“…The expression pattern of ER isoforms has been demonstrated in neoplastic and non-cancerous human thyroid tissues; however, the results are not consistent (19,20). Experimental studies have revealed that estrogen affects PTC development by interacting with ER at the level of target thyroid cells, thereby promoting the proliferation of mutated follicular cells (23). In addition, several different thyroid cancer cell lines have been revealed Tumor size, n (%) to express ER (24)(25)(26), and the proliferation of these cells was stimulated by ERα agonists, and downregulated by ERβ agonists (23).…”

“…Experimental studies have revealed that estrogen affects PTC development by interacting with ER at the level of target thyroid cells, thereby promoting the proliferation of mutated follicular cells (23). In addition, several different thyroid cancer cell lines have been revealed Tumor size, n (%) to express ER (24)(25)(26), and the proliferation of these cells was stimulated by ERα agonists, and downregulated by ERβ agonists (23). Consistently, the present study revealed that the expression of ERα is increased in PTC tissues, compared with the expression in NTG tissues.…”

Oestrogen action on thyroid progenitor cells: relevant for the pathogenesis of thyroid nodules?

“…6), can be explained by the finding that cell growth is primarily regulated via ERa, whereas ERb is involved in the control of apoptosis and suppressive functions (Chen et al 2008). In taking this view, two recent reports that correlated ERa positivity and loss of ERb expression in differentiated thyroid carcinomas with a more aggressive phenotype and a poor outcome are of interest (Heikkila et al 2012, Magri et al 2012.…”

Secular trends in the prognostic factors for papillary thyroid cancer

“…Experimental studies have revealed inhibitory effects of the estrogen receptor beta on the development of thyroid cancer (15,16). A recent epidemiologic study has also demonstrated a better prognosis in younger female patients (!55 years), before menopause, and those aged O55 years had similar outcomes to those of male patients, suggesting a sex disparity in thyroid cancer outcomes (10).…”