title: Reconstituted expression of menin in Men1-deficient mouse Leydig tumour cells induces cell cycle arrest and apoptosis.
abstract: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome caused by the inactivation of the responsible gene, MEN1. To date, the lack of MEN1-deficient cell lines derived directly from MEN1 tumours has hampered the detailed study of the MEN1 gene. We have established several stable Men1-deficient Leydig cell tumour (LCT) lines derived from a Leydig cell tumour developed in a male heterozygous Men1 mutant mouse. Our data show that these cell lines maintain the basic characteristics of Leydig cells in terms of both androgen synthesis and gene expression. Interestingly, reconstituted menin expression in one of Men1-deficient LCT cell lines resulted in cell growth inhibition, suggesting that the function of cell growth suppression of the menin pathway, apart from menin itself, is essentially preserved in these cells. Furthermore, we show that menin re-expression in these Men1-deficient cells leads to a block in the transition from G0/G1 to S phase of the cell cycle and an increase in apoptosis, accompanied by a marked increase of p18INK4C and p27Kip1 expression. The current study therefore highlights the importance of menin expression in cell cycle and cell survival control in endocrine cells, and may provide insights into the mechanisms of tumour suppression by menin in related endocrine tumours.
authors.affiliation: Laboratoire Génétique Moléculaire, Signalisation et Cancer, CNRS, UMR5201, Faculté de Médecine, Université Claude Bernard Lyon 1, 8 Ave. Rockefeller, 69373 Lyon, France.
authors.forename: Nader
authors.initials: N
authors.lastname: Hussein
authors.forename: Huguette
authors.initials: H
authors.lastname: Casse
authors.forename: Sandra
authors.initials: S
authors.lastname: Fontanière
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Morera
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Asensio
authors.forename: Skander
authors.initials: S
authors.lastname: Bakeli
authors.forename: Jie L
authors.initials: JL
authors.lastname: Lu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coste
authors.forename: Nathalie
authors.initials: N
authors.lastname: Di Clemente
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertolino
authors.forename: Chang X
authors.initials: CX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D007150:Immunohistochemistry; D007984:Leydig Cell Tumor / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D051379:Mice; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D011374:Progesterone / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D011374:Progesterone