Role of MLL/menin-cell cycle pathway in neuroendocrine tumorigenesis

Menin是MEN1基因的产物，与混合谱系白血病（MLL）蛋白、人组蛋白甲基转移酶和p27^<Kip1>和p18^<Ink4C>基因的转录激活形成核复合体。在多发性内分泌肿瘤1型（MEN1）中，menin的突变导致p27^<Kip1>和p18^<Ink4C>基因的表达降低，细胞生长失调。我们发现MLL-p27^<Kip1>通路在垂体腺瘤中下调，奥曲肽通过PI3K/Akt和MAPK通路对MLL和p27^<Kip1>基因的顺序转录刺激，至少在一定程度上增加了p27^<Kip1>水平。

Menin, the product of the MEN1 gene, form a nuclear complex with mixed lineage leukemia (MLL) protein, a human histone methyltransferase and activated transcription of the p27^<Kip1> and p18^<Ink4C> genes. In multiple endocrine neoplasia type 1 (MEN1), a mutation of menin caused decreased expression of the p27^<Kip1> and p18^<Ink4C> genes and deregulated cell growth. We found that the MLL-p27^<Kip1> pathway was downregulated in the pituitary adenomas, and octreotide increased the p27^<Kip1> level, at least in part, by sequential transcriptional stimulation of the MLL and p27^<Kip1> genes through PI3K/Akt and MAPK pathways.