The Role Of The Vitamin D Receptor In Anaplastic Thyroid Carcinoma Cells

Objective: Thyroid carcinoma(TC)is the commonest endocrine neoplasms.The incidence rate has steadily increased in the past years.Differentiated thyroid carcinoma is relatively common,with good differentiation and prognosis.However,undifferentiated thyroid carcinoma(also known as anaplastic thyroid carcinoma,ATC)is rare,with poor differentiation,high proliferation and invasiveness,and poor prognosis.The vitamin D receptor(VDR)is highly expressed in DTC,but low or no expression in ATC,suggesting that VDR is associated with the invasion of thyroid carcinoma.The aim of the present study was to clarify the effect of VDR in ATC cells.Methods: We used lentivirus containing VDR-sh RNA to down-regulate VDR in ATC cell line(8505C cells)with relatively high VDR levels and adenovirus containing VDR-c DNA to over-express VDR in ATC cell line(HTh-7 cells)with relatively low VDR levels,respectively.The expression of differentiation markers(NIS、TPO and TSHR)were examined by quantitative real-time polymerase chain reaction(q RT-PCR)and Western blotting analysis.The cell proliferation level was measured by the colony formation assay and5-bromodeoxyuridine(Brd U)incorporation assay.In addition,cell migration was measured by wound healing assay and transwell assay.In order to determine whether the VDR regulates the phosphorylation of protein kinase B(AKT)downstream of phosphatidylinositol-3 kinase(PI3K),the expression levels of AKT and phosphorylated AKT(p-AKT)were measured by Western blotting analysis.Results: Compared to that in DTC cells,the level of VDR expression was decreased in ATC cells.After down-regulating VDR,the expression level of p-AKT increased,the expression level of differentiation markers decreased and the level of proliferation and migration increased.After overexpression of VDR,the expression level of differentiation markers increased,and the level of proliferation and migration decreased.Finally,the expression level of p-AKT increased when VDR was down-regulated in ATC cells,and the expression level of p-AKT decreased when VDR was over-expressed,while the expression level of AKT did not change obviously.Conclusion: VDR inhibits the phosphorylation of AKT,promotes the differentiation and inhibits the proliferation and migration of ATC cells.