Involvement of GCMB in the transcriptional regulation of the human parathyroid hormone gene in a parathyroid-derived cell line PT-r: effects of calcium and 1,25(OH)2D3.
Expression of the PTH gene is known to be under strict tissue-specific control and is also regulated by extracellular calcium and 1,25(OH)(2)D. However, the precise mode of transcriptional regulation remains to be elucidated, because of the unavailability of appropriate cell lines derived from the parathyroid gland. We tried to identify the transcription factor(s) regulating the human PTH gene transcription using the PT-r cell line. We found that PT-r cells endogenously express PTH and several parathyroid-related genes. Using the cells, we investigated the transcriptional regulation of human PTH gene. We found that GCMB binds to the PTH gene 5'-promoter (-390/-383 bp) and positively regulates its transcription. On the other hand, 1,25(OH)(2)D(3), and, in the presence of the calcium sensing receptor, high extracellular calcium, exerted inhibitory effects on PTH gene expression. These results indicate that GCMB and vitamin D receptor are involved in the positive and negative regulation of PTH gene expression, respectively. Our data also suggest that PT-r cells retain some of the characteristics of parathyroid cells.
Kawahara
Masayuki
M
Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku 783-8505, Japan.
Iwasaki
Yasumasa
Y
Sakaguchi
Kazushige
K
Taguchi
Takafumi
T
Nishiyama
Mitsuru
M
Nigawara
Takeshi
T
Kambayashi
Machiko
M
Sawada
Takahiro
T
Jing
Xuefeng
X
Miyajima
Masayasu
M
Terada
Yoshio
Y
Hashimoto
Kozo
K
Suda
Toshihoro
T
D001483:Base Sequence; D050071:Bone Density Conservation Agents / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010280:Parathyroid Glands / Q000166:cytology*; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D050071:Bone Density Conservation Agents; C119532:GCM2 protein, human; D009687:Nuclear Proteins; C470125:PTH protein, human; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D002117:Calcitriol; D002118:Calcium