Increased MEN1 mRNA expression in sporadic pituitary tumours.

Abstract

The MEN1 gene on chromosome 11q13 encodes a tumour suppressor gene, mutations in which cause multiple endocrine neoplasia (MEN) type 1 syndrome. Loss of heterozygosity (LOH) at this locus is a common finding amongst sporadic pituitary tumours. We have therefore screened the MEN1 gene for mutations in sporadic pituitary tumours and, as the gene is a putative tumour suppressor, have quantified mRNA expression in tumorous and normal pituitaries to assess the role of MEN1 in pituitary tumorigenesis. Thirty-one nonfunctioning pituitary tumours, 8 GH secreting, 2 TSH-secreting tumours and 1 corticotrophinoma have been assessed for the presence of MEN1 mutations, to examine the hypothesis that MEN1 mutations may contribute to the pathogenesis of sporadic pituitary neoplasms. In addition, quantitative changes in the pretranslational expression of the tumour suppressor gene MEN1 have been determined in 42 pituitary tumours and 6 normal pituitaries using semiquantitative reverse transcriptase PCR. No novel or previously published mutations were apparent in the MEN1 coding regions of any tumours studied, although several polymorphisms were identified. Transcriptional changes of the gene, assessed by semiquantitative RT-PCR, indicated that nonfunctioning and GH-secreting pituitary tumours are associated with significantly increased pretranslational expression of the MEN1 gene. In addition, the single corticotrophinoma showed increased expression compared to normal, as did one of the two TSH-omas. Coding mutations of the putative tumour suppressor gene MEN1 are unlikely to contribute to pituitary tumorigenesis in sporadic nonfunctioning, GH-secreting and TSH-secreting adenomas. Changes in pretranslational expression of MEN1 were observed in pituitary tumours, suggesting that changes in the level of MEN1 expression, rather than coding changes, may be of functional importance in influencing sporadic pituitary tumorigenesis.