Endocrine Abstracts

Several studies indicated that estrogen receptors (ERs) and vitamin D receptor (VDR), as well 1α-hydroxylase 25-hydroxy vitamin D (1OHase) are expressed in various normal and cancerous cell types. To date, there are no reported studies on the different expressions of VDR, 1OHase and ERs, in human thyroid normal and cancer cells. This study addresses these questions. Tissues harvested from papillary thyroid cancer (PTC) and normal glands explants were used throughout either as intact explants or as cell cultures. The relative VDR, 1OHase and ERα, ERβ, in these samples were determined by real time PCR. Both normal thyroid and PTC explants and cultured cells expressed VDR and 1OHase mRNA as well as ERα and ERβ. Cancer thyroid explants had higher abundance than normal ones of VDR, ERβ and ERβ but lower 1OHase. Cancer thyroid cultured cells had higher abundance than normal ones of VDR, ERα and ERβ but lower 1OHase. When cultured normal and cancer cells where treated with 0.1 nM of 1,25(OH)₂D₃ (1,25D) or 1nM the less calcemic vitamin D analog (JKF) or the non calcemic analog (CB) there is increased mRNA expression in cancer cells of ERα, ERβ, VDR and 1OHase, whereas in normal cells the stimulations were to lower extent. In conclusion thyroid cancer and normal explants as well as cultured cells from these tissues, express mRNA for VDR and 1OHase as well as different ERs, to different extent and are modulated by 1,25D or the vitamin D analogs. These results are similar to those obtained with human thyroid cancer cell lines. This might form the basis for the use of hormonal modulation of different mRNAs for therapy and affinity drug targeting via VDR, 1OHase and/or ERs by controlling their levels. These results are consistent with the hypothesis that endogenous vitamin D and estrogens may affect thyroid cancer cell growth via opposing pathways: cell growth acceleration via induction of ER expression, in association with the induction of VDR and 1OHase to promote the synthesis of 1,25D which is known to inhibit cell proliferation via binding to VDR. This is the first report describing direct regulation of VDR and 1OHase expression by vitamin D compounds in primary cultured human thyroid cancer cells. A functional role for vitamin D system in human thyroid cancer is suggested by the finding that the vitamin D compounds can affect ERs expression which is in turn involved in estrogen-induced cell growth in an ER-type specific manner.