CRABP2 expression is up-regulated in parathyroid adenomas in correlation with HRPT2 down-regulation
Jadwiga Zebracka1, Janusz Waler2, Malgorzata Kowalska1, Grzegorz Gala1, Jacek Gawrychowski2 & Barbara Jarzab1
Introduction: The molecular events involved in the formation of parathyroid adenomas are not well understood. Two genes, cyclin D1 (CCND1) and MEN-1, have been established as having major roles in parathyroid tumorigenesis. Tumor suppressor gene HRPT2 is frequently mutated in parathyroid carcinoma. The aim of our study was to analyze HRPT2 expression in parathyroid adenomas and in residual normal/atrophic parathyroid tissue and to relate it to other molecular markers CCND1 (cyclin D1) and MEN-1 expression. We also put the question whether CRABP2 (cellular retinoic acid binding protein 2), a gene selected on the basis of the microarray study by Forsberg et al., 2005, does show the change in expression in parathyroid adenomas when analyzed by Q-PCR.
Material and methods: The analysis of HRPT2, CRABP2, c-JUN, CCND1 and MEN-1 was carried out in 19 parathyroid adenomas taken intraoperatively, and 56 normal/atrophic parathyroid samples. Analysis of gene expression was performed by real-time quantitative PCR (QPCR) with the use of fluorescent probes, based on 5′-nuclease assay (TaqMan). Expression of the examined genes was normalized to the reference index, obtained by calculation of geometric mean of reference genes expression: EIF3S10, UBE2D2 and ATP6V1E.
Results: We observed a 1.5-fold, non significant decrease of HRPT2 expression in adenomas in comparison to normal/atrophic parathyroids. The expression of the gene was significantly correlated with c-JUN expression but not with CCND1 and MEN-1. CRABP2 expression was significantly increased (P<0.05) in adenomas and the change in expression (mean: 1.3-fold) was correlated with HRPT2 expression.
Conclusion: CRABP2 expression is up-regulated in parathyroid adenomas in correlation with HRPT2 down-regulation.