Abstract
Preceding studies have indicated that aberrant expression levels rather than genetic
changes of GADD45γ, MEG3, and p8 gene might play a role in the pathogenesis of pituitary
adenomas. We analysed their expression in various normal human tissues and in different
pituitary tumour types, and investigated GADD45γ mutations in a subset of adenomas.
Absolute quantification by real-time RT-PCR was performed in 24 normal tissues as
well as in 34 nonfunctioning, 24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas,
1 FSHoma, and in 6 normal pituitaries. Furthermore, we investigated the relationship
between clinical data and gene expression. A subset was screened for GADD45γ mutations
by single strand conformation polymorphism analysis (SSCP) and sequencing. All normal
human tissues expressed GADD45γ, MEG3, and p8 mRNA. For GADD45γ, significantly lower
expression levels were found in nonfunctioning adenomas compared with normal pituitary
and somatotroph adenomas. P8 and MEG3 mRNA levels were significantly lower in nonfunctioning
and corticotroph adenomas compared with normal pituitary. Expression of GADD45γ was
significantly higher in pituitary adenomas of female patients. No mutation was found
in the GADD45γ gene. GADD45γ, MEG3, and p8 appear to have physiological functions
in a variety of human tissues. GADD45γ, MEG3, and P8 may be involved in the pathogenesis
of nonfunctioning and corticotroph pituitary tumours. Female gender seems to predispose
to slightly higher GADD45γ expression in pituitary adenomas. Mutations of the GADD45γ
are unlikely to be involved in the pathogenesis of pituitary adenomas.
Key words
growth arrest and DNA damage-inducible gene 45γ - maternally expressed gene 3 - protein
8 - mutation - polymorphism - pituitary tumour
