Taken together, our results suggest that Menin functions as an oncogene for cancer metastasis upon C/EBPβ depletion or acts as a tumor suppressor by cooperation with C/EBPβ to activate CDKN2A transcription.
The concordance of menin staining between primary tumor and metastasis in most cases suggests that menin loss is an early event in PanNET tumorigenesis.
In the present study, miR‑24 was found to be associated with menin, affecting the activity of the SMAD3 pathway in lung cancer by inhibiting menin expression. miR‑24 may promote the growth and metastasis and inhibit the apoptosis of lung cancer cells by targeting menin.
Patients with carcinoids harboring MEN1 mutation and loss had shorter overall survival (P = .039 and P = .035, respectively) and low MEN1 mRNA levels correlated with distant metastasis (P = .00010) and shorter survival (P = .0071).
We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib.
Thymic neuroendocrine tumour (Th-NET) occurs in 2-5% of patients with MEN1 and has high malignant potency accompanying recurrence and distant metastasis.
Menin expression is reduced in certain human non-small cell lung cancer cells, and reduction of menin is closely correlated with increased lung cancer metastasis to lymph nodes.
Previous molecular studies have shown that gain of chromosome 9q rather than MEN1 gene mutation is an important early event in tumour development and that chromosomal instability is associated with metastatic disease.
A total of 119 transcripts were underexpressed < or =3-fold in PENs compared with normal islet cells, including cell cycle checkpoint proteins (p21/Cip1), the MIC2 (CD99) cell surface glycoprotein, putative metastasis suppressor genes (NME3), and junD, a MEN1-regulated transcription factor.
We conclude that sporadic gastrinomas at multiple sites are monoclonal and that MEN1 gene alterations in gastrinomas occur before the development of tumor metastases.
To assess whether the MEN1 region is involved in tumour initiation and progression, we analysed 23 primary cutaneous melanomas and 17 metastases for loss of heterozygosity (LOH) using two informative polymorphic markers closely linked to the MEN1 gene (PYGM and D11S449).
We used tissue microdissection to analyze 95 archival pancreatic and duodenal ETs and metastases from 50 patients for loss of heterozygosity (LOH) on 11q13 with 10 polymorphic markers spanning the area of the putative MEN1 gene.
In patients with ZES, increased PP levels were not related to the presence of MEAI or metastases; nor was there a correlation between serum PP and gastrin concentrations.