GCMB gene, a master regulator of parathyroid gland development, expression, and regulation in hyperparathyroidism.
BACKGROUND
The glial cell missing gene, GCMB , encodes a transcription factor, which is a master regulator of parathyroid development. We postulated that the GCMB gene might play a role in parathyroid tumorigenesis in hyperparathyroidism.


METHODS
We used real-time quantitative reverse transcriptase polymerase chain reaction to study GCMB mRNA expression in parathyroid tissue: normal (n = 3), hyperplastic (n = 16), adenomas (n = 19), and cancers (n = 8). In primary parathyroid culture, the effect of CaCl 2 on parathyroid hormone secretion and GCMB mRNA expression was studied by using enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction, respectively.


RESULTS
GCMB mRNA expression was lower in normal (0.4 +/- 0.1, mean +/- standard error of mean) parathyroid glands as compared to adenoma (3.5 +/- 1.7), hyperplasia (3.2 +/- 1.3 primary hyperparathyroidism [n = 11] and 7.6 +/- 4.8 secondary hyperparathyroidism [n = 5]), and cancer (3.6 +/- 1.3) ( P = .001). There was no difference in the level of GCMB mRNA expression between parathyroid adenoma, hyperplasia, and cancer. In primary culture of parathyroid adenoma (n = 9) and hyperplasia (n = 2), parathyroid hormone secretion was increased 2- to 15-fold with low calcium concentration (0.5 to 4.0 mmol/L CaCl 2 from 2 to 6 hours, P < .005). The level of GCMB mRNA expression was down-regulated with lower extracellular CaCl 2 concentration ( P < .005).


CONCLUSIONS
GCMB expression is upregulated in abnormal parathyroid glands of hyperparathyroidism and decreases in response to hypocalcemia. The GCMB transcription factor might mediate the effect of calcium on parathyroid cell parathyroid hormone expression/secretion.
Kebebew
Electron
E
Department of Surgery, University of California-San Francisco, Box 1674, San Francisco, CA 94143, USA.
Peng
Miao
M
Wong
Mariwil G
MG
Ginzinger
David
D
Duh
Quan-Yang
QY
Clark
Orlo H
OH
D000236:Adenoma / Q000235:genetics; D000368:Aged; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics; D006965:Hyperplasia / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics*; D009687:Nuclear Proteins; D010279:Parathyroid Diseases / Q000235:genetics*; D010280:Parathyroid Glands / Q000502:physiology*; D010282:Parathyroid Neoplasms / Q000235:genetics; D014157:Transcription Factors
C119532:GCM2 protein, human; D009479:Neuropeptides; D009687:Nuclear Proteins; D014157:Transcription Factors