Am J Cancer Res 2011;1(6):726-739

Review Article
Menin represses tumorigenesis via repressing cell proliferation

Ting Wu, Xianxin Hua

Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, China; Abramson Family Cancer Research
Institute, Department of Cancer Biology, the University of Pennsylvania, School of Medicine, 421 Curie Blvd., Philadelphia, PA
19104, U.S.A..

Received April 20, 2011; accepted May 8, 2011; Epub May 16, 2011; Published June 30, 2011

Abstract: Multiple endocrine neoplasia type 1 (MEN1) results from mutations in the tumor suppressor gene, MEN1, which
encodes nuclear protein menin. Menin is important for suppressing tumorigenesis in various endocrine and certain non-
endocrine tissues. Although menin suppresses MEN1 through a variety of mechanisms including regulating apoptosis and DNA
repair, the role of menin in regulating cell proliferation is one of the best-studied functions. Here, we focus on reviewing various
mechanisms underlying menin-mediated inhibition of cell proliferation. Menin inhibits cell proliferation to repress MEN1 through
multiple mechanisms. 1) Menin interacts with various histone-modifying enzymes, such as MLL, EZH2 and HDACs, to affect
gene transcription, leading to repression of cell proliferation. 2) Menin also interacts with various transcription factors, such as
JunD, NF-кB, PPARγ and VDR, to induce or suppress gene transcription. As these various transcription factors are known to
regulate cell proliferation, their interaction with menin may be relevant to menin’s role in inhibiting cell proliferation. 3) Menin
inhibits cell proliferation via TGF-β signaling and Wnt/β-catenin signaling pathways. 4) Menin represses certain pro-proliferative
factors involved in endocrine tumors such as IGFBP-2, IGF2 and PTHrP to repress cell proliferation. 5) Menin affects cell cycle
progression to inhibit cell proliferation. This review is helpful in our understanding of the comprehensive mechanisms whereby
menin represses MEN1 through inhibiting cell proliferation. (AJCR0000063).

Keywords: Menin, cell proliferation, gene transcription, epigenetics, cell cycle

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Address all correspondence to:
Dr. Xianxin Hua
Abramson Family Cancer Research Institute
Department of Cancer Biology
The University of Pennsylvania School of Medicine
421 Curie Blvd., Philadelphia, PA 19104, USA.
Tel: 215-746-5565,
E-mail:
huax@mail.med.upenn.edu
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American Journal of Cancer Research
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