Vitamin D less-calcemic analog modulates the expression of estrogen receptors, vitamin D receptor and 1α-hydroxylase 25-hydroxy vitamin D in human thyroid cancer cell lines.
Estrogen receptors (ERs) are expressed in various "non-reproductive" cancer cell types. Some cancer types express 1α-hydroxylase 25-hydroxy vitamin D (1OHase) whose product, 1,25(OH)2D3 can retard cancer cell proliferation. Thyroid carcinoma cell growth is apparently promoted by estrogens, but whether or not this interaction is modified by vitamin D metabolites/analogs is presently unknown. Here we assessed the effect of a less calcemic vitamin D analog [JK 1624 F2-2 (JKF)] in three human thyroid cancer cell lines: ARO (anaplastic carcinoma), NPA (papillary carcinoma) and MRO (follicular carcinoma). (1) All cell lines expressed both ERα and ERβ, vitamin D receptor (VDR) and 1OHase mRNA quantified by Real Time PCR. There was a general abundance of ERβ over ERα expression, such that the ratio of ERβ to ERα mRNA was >1000:1, 228:1 and 7.7:1 in ARO, MRO and NPA cells, respectively. (2) JKF up regulated ERβ expression in ARO (by 110±15%) and MRO (by 280±10%) but down regulated ERβ in NPA cells (by 40±15%). The expression of VDR was up regulated by JKF in NPA (21±6%), down regulated in ARO (-24±7%) and not affected in MRO. (3) All three human thyroid cancer cell lines were found to express 1OHase, which was up regulated by JKF in MRO (350±25%) and NPA (35±8%) but down regulated in ARO (-20±5%). This is the first report to describe direct regulation of VDR and 1OHase expression by a vitamin D analog in human thyroid cancer cells. A functional role for the vitamin D system in human thyroid cancer is suggested by the finding that the vitamin D analog can affect ERs expression which is in turn involved in estrogen-induced cell growth in an ER-type specific manner in these cells.
Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. dalias@tasmc.health.gov.il
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D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C113642:JK 1624F2-1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018167:Receptors, Calcitriol; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol