Menin has been shown negatively to regulate transcriptional activation mediated by JunD, although the significance of this interaction in normal cell physiology and how the absence of menin leads to tumorigenesis are unknown.Menin is highly expressed in testes.
Menin displays the unique ability to either promote oncogenic function in the hematopoietic lineage or suppress tumorigenesis in the endocrine lineage; however, its molecular mechanism of action has not been defined.
Menin's interaction with mixed-lineage leukemia protein-containing histone methyl transferase (MLL-HMT) complex mediates tissue-selective tumor-suppressing and tumor-promoting effects of menin, and as such could be decisive for the predisposition of individual tissues to MEN1-associated tumorigenesis.
Menin plays some physiological and pathological roles related to transforming growth factor-beta (TGF-β) signaling pathway in the parathyroid, and it is implicated in the tumorigenesis of parathyroid tumors.
Alleotyping showed loss of heterozygosity (LOH) involving the wild-type alleles in seven tumors in the family including the ependymoma, which is the first MEN1-related case that shows genetic abnormality in chromosome 11q13, suggesting that MEN1 gene might be involved in the tumorigenesis of a subset of ependymomas.
Among others, loss of the short arm of chromosome 1 and somatic inactivation of the multiple endocrine neoplasia type 1 gene (MEN1) in 11q13 represent significant alterations in the tumorigenesis.
Apart from inactivation of the MEN1 gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated non-endocrine lesions remain unknown.
Apart from inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene, the molecular mechanisms involved in tumorigenesis of the endocrine organs and MEN1-associated nonendocrine lesions are vastly unknown.
Based on the type of mutation, we discuss possible changes in menin function leading to atypical tumorigenesis and present the clinical significance of such findings.
Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN1 region, we have investigated the involvement of the MEN1 gene in melanoma tumorigenesis.
Based on these, it is concluded that inactivation of the MEN1 gene comprises a rare etiology for tumorigenesis of the pituitary gland, and that trisomy 11 or another gene(s) may contribute to the pathogenesis of sporadic pituitary adenomas.
Because the frequency of mutations varies significantly among the investigated tumor subgroups and allelic deletions are 2 to 3 times more frequently observed, factors other than MEN1 gene inactivation, including other tumor-suppressor genes on 11q13, may also be involved in the tumorigenesis of these neoplasms.
Biallelic inactivation of MEN1 encoding menin in pancreatic neuroendocrine tumors (PNETs) associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome is well established, but how menin loss/inactivation initiates tumorigenesis is not well understood.
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.
Conditional knockout of β-catenin suppresses the tumorigenesis and growth of Men1-deficient PNETs, and significantly prolongs the survival time in mice.
Delineation of the genetic events leading to neoplastic transformation of islet cells is at an early stage; but based on tumor deletion studies, it appears that inactivation of the MEN 1 gene is an early step in carcinogenesis for both sporadic and MEN 1-related tumors.
Epigenetic profiling and gene expression analysis in Men1-deficient pancreatic islet cells reveals vital insight into the molecular events that occur during the progression of pancreatic islet tumorigenesis.