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Expression and Function of Cbfa-1/Runx2 in Thyroid Papillary Carcinoma Cells

Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi 409-3898, Japan

Address all correspondence and requests for reprints to: Dr. Toyoshi Endo, M.D., Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi 409-3898, Japan. E-mail: endot{at}yamanashi.ac.jp.

Context: Development of calcifying foci is a common finding in human thyroid papillary carcinoma, but its mechanisms remain unknown.

Objective: We therefore investigated whether osteocalcin and/or Cbfa-1 genes are expressed in malignant thyroid epithelial cells. We also studied the effects of Cbfa-1 on the expression of osteoblast-specific and thyrotropin receptor genes in thyrocytes.

Results: The human thyroid papillary carcinoma cell line BHP18–21 expresses bone-type osteocalcin mRNA at higher levels than in MG63 osteosarcoma cells. Northern blot analysis and EMSA using nuclear extracts from BHP18–21 cells and FRTL-5 cells demonstrated that cells of thyroid epithelial origin expressed Cbfa-1/Runx2, the main transcription factor for the expression of osteocalcin. When we transfected pcDNA3.1-human Cbfa-1 into FRTL-5 cells, Cbfa-1 increased the gene expression of alkaline phosphatase, type I collagen, and osteocalcin but suppressed the expression of thyrotropin receptor. We then stained the calcified regions of human papillary thyroid carcinoma tissues with antiosteocalcin antibody and found that malignant cells, as well as follicular epithelial cells, were immunopositive for osteocalcin. Northern blot analysis revealed that the Cbfa-1/Runx2 gene was strongly expressed in tissues from four cases of surgically resected papillary carcinoma.

Conclusions: Thyrocytes share characteristics with osteoblasts. Cbfa-1 may play a role in calcification processes in human thyroid papillary carcinoma tissues.