ABSTRACT Menin upregulates transcription of cell-cycle inhibitors to suppress endocrine tumors, but it is poorly understood how menin suppresses non-endocrine tumors such as lung cancer.

Here, we show that menin inhibits proliferation of human lung cancer cells and growth of lung cancer in mice. The menin-mediated tumor suppression requires repression of growth factor

pleiotrophin (PTN), which binds to its cell surface receptor, anaplastic lymphoma kinase (ALK) that is activated in certain lung adenocarcinomas. Menin represses _PTN_ transcription and

PTN-induced proliferation of human lung cancer cells, and menin expression is substantially reduced in primary human lung adenocarcinomas. Notably, menin binds the _PTN_ locus and enhances

and repressing _PTN_ transcription, unraveling a novel, epigenetically regulated PTN–ALK signaling pathway in suppressing lung cancer. Access through your institution Buy or subscribe This

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maintenance factor in morphogenesis. _Proc Natl Acad Sci USA_ 95: 10632–10636. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work is in partly supported by NFSC

Grants (No 30701003, GH Jin), the Natural Science Foundation of Fujian Province of China (No C0710044, GH Jin), National Cancer Institute Short-Term Scientist Exchange Program (GH Jin), and

National Cancer Institute Grants (R01CA100912 and R01CA113962, XH). We appreciate the valuable comments from other members of our laboratories. AUTHOR INFORMATION Author notes * S-B Gao and

Z-J Feng: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China S-B

Gao, Z-J Feng, B Xu, Y Wu, X Hua & G-H Jin * Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, PR China P Yin * Department of Cancer Biology, University of

Pennsylvania, Philadelphia, PA, USA Y Yang & X Hua Authors * S-B Gao View author publications You can also search for this author inPubMed Google Scholar * Z-J Feng View author

publications You can also search for this author inPubMed Google Scholar * B Xu View author publications You can also search for this author inPubMed Google Scholar * Y Wu View author

publications You can also search for this author inPubMed Google Scholar * P Yin View author publications You can also search for this author inPubMed Google Scholar * Y Yang View author

publications You can also search for this author inPubMed Google Scholar * X Hua View author publications You can also search for this author inPubMed Google Scholar * G-H Jin View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to X Hua or G-H Jin. ADDITIONAL INFORMATION Supplementary Information

accompanies the paper on the Oncogene website (http://www.nature.com/onc) SUPPLEMENTARY INFORMATION SUPPLEMENTARY MATERIALS AND METHODS (DOC 44 KB) SUPPLEMENTARY FIGURES AND TABLES (DOC 418

KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gao, SB., Feng, ZJ., Xu, B. _et al._ Suppression of lung adenocarcinoma through menin and polycomb

gene-mediated repression of growth factor pleiotrophin. _Oncogene_ 28, 4095–4104 (2009). https://doi.org/10.1038/onc.2009.273 Download citation * Received: 13 May 2009 * Accepted: 31 July

2009 * Published: 14 September 2009 * Issue Date: 19 November 2009 * DOI: https://doi.org/10.1038/onc.2009.273 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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initiative KEYWORDS * lung adenocarcinoma * histone H3 lysine 27 * _Men1_ * pleiotrophin * Polycomb