Expression of folate receptor is down-regulated in somatotropinomas
Jadwiga Zebracka1, Adam Rudnik2, Kornelia Hasse Lazar1, Dawid Larysz2, Michal Jarzab3, Beata Lubieniecka1, Grzegorz Gala1 & Barbara Jarzab1
Introduction: Pathogenesis of pituitary adenomas is largely unknown thus, identification of genes specific for various types of pituitary tumors should enable better understanding of their biology.
The aim of our study was to analyze differences in gene expression between functional (FA) and non-functional (NFA) pituitary adenomas. For this goal, we considered folate receptor (FOLR1) shown by previous study (Evans et al. 2003) to be overexpressed in NFA, as well as some other genes reported for its changed expression.
Material and methods: Analysis of gene expression was performed by real-time quantitative PCR (QPCR) with the use of fluorescent probes, based on 5′-nuclease assay (TaqMan). Within the 54 pituitary adenomas collected there were 16 nonfunctioning and 38 functioning ones, among them 7 GH and 13 PRL- secreting adenomas. Expression of the examined genes was normalized to the reference index, obtained by calculation of geometric mean of reference genes expression: GUS-B, B2M, ACTB, EIF3S10, UBE2D2 and ATP6V1E.
Results: Folate receptor gene (FOLR1) was not significantly overexpressed in NFA compared with FA but was significantly overexpressed when NFA were compared to GH (but not PRL) adenomas. Also, we observed a 3-fold decrease of CCND1 expression in GH adenomas compared with NFA. Again, the change in expression was not significant at the comparison PRL/NFA. hPTTG1 and MEN1 expression was similar in all tumors analyzed.
Conclusions: Folate receptor expression and cyclin D1 expression are down-regulated in somatotropinomas when compared to non-functioning pituitary tumors while prolactinomas do not show such a distinct change in their expression.