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 (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.