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Increased MEN1 mRNA expression in sporadic pituitary tumours
C J McCabe1, N J Gittoes, M C Sheppard
1Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
Clinical Endocrinology
|September 1, 1999
Summary
Mutations in the MEN1 gene do not cause sporadic pituitary tumors. However, altered MEN1 gene expression is linked to pituitary tumor development, suggesting expression levels are key in tumorigenesis.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- The MEN1 gene, located on chromosome 11q13, encodes a tumor suppressor protein implicated in Multiple Endocrine Neoplasia type 1 syndrome.
- Loss of heterozygosity (LOH) at the MEN1 locus is frequently observed in sporadic pituitary tumors.
- Investigating MEN1's role in pituitary tumorigenesis is crucial given its tumor suppressor function.
Purpose of the Study:
- To screen sporadic pituitary tumors for MEN1 gene mutations.
- To quantify MEN1 mRNA expression in pituitary tumors and normal pituitary tissue.
- To assess the role of MEN1 in pituitary tumorigenesis.
Main Methods:
- Screening of MEN1 coding regions for mutations in 42 sporadic pituitary tumors (31 nonfunctioning, 8 GH-secreting, 2 TSH-secreting, 1 corticotrophinoma).
- Quantitative analysis of MEN1 pretranslational mRNA expression using semiquantitative reverse transcriptase PCR (RT-PCR) in 42 pituitary tumors and 6 normal pituitaries.
- Assessment of MEN1 polymorphisms in tumor DNA.
Main Results:
- No MEN1 coding mutations were detected in any of the studied pituitary tumors; several polymorphisms were identified.
- Significantly increased pretranslational expression of the MEN1 gene was observed in nonfunctioning and GH-secreting pituitary tumors compared to normal tissue.
- Elevated MEN1 expression was also noted in the single corticotrophinoma and one TSH-secreting tumor.
Conclusions:
- Coding mutations in the MEN1 tumor suppressor gene are unlikely to be a primary driver of sporadic nonfunctioning, GH-secreting, or TSH-secreting pituitary adenomas.
- Observed alterations in MEN1 pretranslational expression suggest that changes in gene expression levels, rather than coding mutations, may play a significant role in sporadic pituitary tumorigenesis.
- Further research into the regulatory mechanisms of MEN1 expression in pituitary tumors is warranted.