The Roles Of Menin Expression Dosage In Regulating Tumor Cell Growth

Menin is encoded by a tumor suppressor gene MENI,which is expressed very extensively nearly in all tissues.Mutations in this gene cause multiple endocrine gland tumors.But the function of Menin is still unknown and how its mutations leading to endocrine tissue tummors is also still unknown,though various hypothesis for its roles have been raised.In this paper,we described that knocking-down Menin by lentivirus to monitor the effect of gene expression dosage of MEN1 on cell cycles and early response genes under milieu with or without certain endocrine hormones in B16F1 cells.We successfully obtained several pLKO.1-shRNA-MEN1 constructs,with Menin expression dosage as Scrambl,368,394,395,396,397 in B16F1.Scramble,141,142,140 in HepG2.Our results indicated that both the expression of early response genes and cell cycle genes were altered by Menin in a dosage dependent manner.For the first time,we found the expression of various early response genes,as Egrl,JunD,C-myc,C-Jun and C-Fos were altered upon Menin knocking-down.Secondly,low express level of Menin can inhibit cell proliferation also induce cell apoptosis no matter in B16F1 and HepG2 cell line.But inuslin and FSK treatment can partial rescue the cell proliferation inhibition and cell apoptosis.Thirdly we found that low dose Menin inhibited cell proliferation with more cells being blocked at G1 phase with shortened S or G2/M phase,and also promoted cell apoptosis in B16F1 cell line.Notably,different knocking down efficiency may have distinct consequences for cells.