Regulation of cell growth by estrogen signaling and potential targets in thyroid cancer

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 (ER alpha) and estrogen receptor beta (ER beta) both of which are known to be expressed in thyroid cancer cells. The proliferation of thyroid cancer cells is promoted by an ER alpha agonist, whereas the proliferation is reduced by the enhanced expression of ER beta or by an ER beta agonist. When ER beta is down-regulated, the proliferation of thyroid cells is significantly increased. Studies have shown that the expression of ER alpha in thyroid cancer cells is increased while the expression of ER beta 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 ER alpha and ER beta in the cells. The modulation of ER alpha and ER beta and the intervention of their pathways may open up new potential targets for the treatment of thyroid cancer.