Underexpression of Gcm2, a master regulatory gene of parathyroid gland development, in adenomas of primary hyperparathyroidism.

Abstract

Glial cells missing (Gcm) was first identified as a binary switch between neuronal and glial determination in Drosophila. Two homologues of Drosophila Gcm have been identified in mice and humans, namely Gcm1 and Gcm2. Mouse Gcm2 is restricted to parathyroid tissues and Gcm2 was recently identified as a master regulatory gene of parathyroid gland development as Gcm2 knockout mice lack parathyroid glands. To identify Gcm2 transcripts in human non-neural tissues and to examine whether Gcm2 is involved in parathyroid gland tumorigenesis we analysed Gcm2 transcript levels in several non-neural tissues by reverse transcriptase polymerase chain reaction (RT-PCR) and performed real-time quantitative RT-PCR analysis on five normal glands, 15 parathyroid adenomas of primary hyperparathyroidism (HPT) and nine hyperplastic glands of secondary HPT. We found high Gcm2 mRNA expression in human parathyroid glands in comparison with other non-neural tissues and underexpression in parathyroid adenomas but not in lesions of HPT secondary to uraemia. Because adenomas demonstrate lower Gcm2 expression than normal glands we suggest that reduced expression of Gcm2 contributes to parathyroid gland tumorigenesis. We speculate that a proper expression level of the Gcm2 transcription factor could be important for maintaining a fully differentiated state of the parathyroid cell.