Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.

OBJECTIVES

The study was designed to evaluate expression profiling of mitogen-activated protein kinase (MAPK) signalling pathway genes in sporadic parathyroid adenoma.

METHODS

Expression of MAPK signalling pathway genes including activated transcription factors and cell cycle regulatory genes was analysed by real-time PCR- based array in parathyroid adenoma (N = 20) and normal parathyroid tissue (N = 4).

RESULTS

MAPK signalling pathway as studied by PCR array revealed that a total of 22 genes were differentially expressed (≥ twofold change, p ≤ 0.05) in parathyroid adenoma. Up-regulated genes were ARAF, MAPK12, CREBBP, MYC, HSPB1, HRAS, CDK4, CCND1, and E2F1, and down-regulated genes were MAP4K1, DLK1, MAP3K4, MAPK10, MAPK8, ATF2, SMAD4, MEF2C, LAMTOR3, FOS, CDKN2A CDKN2B, and RB1. The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma. Expression of CDK4 was positively associated with plasma PTH level (r = 0.60, p = 0.04) and tumor weight (r = 0.80, p = 0.02) of the adenoma patients, respectively. Expression of CDKN2A was correlated negatively with PTH level (r = - 0.52, p = 0.04) of the adenoma patients.

CONCLUSION

The current study revealed that ERK pathway and associated cell cycle regulator genes are dysregulated in sporadic parathyroid adenoma.