Expression and subcellular localization of menin in human cancer cells

Ren,Feng; Xu,Hong-Wei; Hu,Yu; Yan,Shuang-Hong; Wang,Feng; Su,Bao-Wei; Zhao,Qi

doi:10.3892/etm.2012.530

Expression and subcellular localization of menin in human cancer cells

Authors:
- Feng Ren
- Hong-Wei Xu
- Yu Hu
- Shuang-Hong Yan
- Feng Wang
- Bao-Wei Su
- Qi Zhao
View Affiliations

Affiliations: Department of Clinical Laboratory, The Fourth People's Hospital of Wuxi, Wuxi, Jiangsu 214062, P.R. China, Department of General Surgery, The Fourth People's Hospital of Wuxi, Wuxi, Jiangsu 214062, P.R. China
Published online on: March 29, 2012 https://doi.org/10.3892/etm.2012.530
Pages: 1087-1091

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of this study was to elucidate the expression and localization of menin, a protein encoded by the multiple endocrine neoplasia type I (MEN1) gene, in 13 human cancer cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression of the menin gene. The localization of the menin protein was detected by immunofluorescence microscopy. Western blotting was used to determine the quantity of menin in the nucleus, cytosol and membrane of the cells. RT-PCR revealed that menin was expressed in all the cell lines examined in this study. Immunofluorescence microscopy revealed that menin was located primarily in the nucleus. In the GES-1 (transformed human gastric epithelium), MCF-7 (breast cancer), SGH44 (brain glioma) and HeLa (cervical cancer) cell lines, menin was also found to be localized to the membrane, cytosol and nucleus. Moreover, in SGH44 cells more menin was located in the cytosol than the nucleus. Similar findings were obtained by western blotting. In the GES-1 and MKN-28 cells undergoing octreotide treatment, cytoplasmic menin was significantly increased compared with the control groups. Therefore, we suggest that menin is expressed in a number of human cancer cell lines and that the cytosolic distribution increases when the cells undergo octreotide treatment, indicating a new role for menin.

View Figures

View References

1.	Wu T and Hua X: Menin represses tumorigenesis via repressing cell proliferation. Am J Cancer Res. 1:726–739. 2011.PubMed/NCBI
2.	Pannett AA and Thakker RV: Multiple endocrine neoplasia type 1. Endocr Relat Cancer. 6:449–473. 1999. View Article : Google Scholar
3.	Tsukada T, Nagamura Y and Ohkura N: MEN1 gene and its mutations: basic and clinical implications. Cancer Sci. 100:209–215. 2009. View Article : Google Scholar : PubMed/NCBI
4.	Feng ZJ, Gao SB, Wu Y, Xu XF, Hua X and Jin GH: Lung cancer cell migration is regulated via repressing growth factor PTN/ RPTP β/ζ signaling by menin. Oncogene. 29:5416–5426. 2010.PubMed/NCBI
5.	Hory B and Drüeke TB: Menin and MEN 1 gene: a model of tumour suppressor system. Nephrol Dial Transplant. 13:2176–2179. 1998. View Article : Google Scholar : PubMed/NCBI
6.	Yang Y and Hua X: In search of tumor suppressing functions of menin. Mol Cell Endocrinol. 265–266:34–41. 2007.PubMed/NCBI
7.	Guru SC, Goldsmith PK, Burns AL, et al: Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA. 95:1630–1634. 1998. View Article : Google Scholar : PubMed/NCBI
8.	Lopez-Egido J, Cunningham J, Berg M, Oberg K, Bongcam-Rudloff E and Gobl A: Menin’s interaction with glial fibrillary acidic protein and vimentin suggests a role for the intermediate filament network in regulating menin activity. Exp Cell Res. 278:175–183. 2002.
9.	Yan J, Yang Y, Zhang H, et al: Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells. Oncogene. 28:973–982. 2009. View Article : Google Scholar : PubMed/NCBI
10.	Chen YC, Ren F, Sang JR, Tao Y and Xu WR: Type II cGMP-dependent protein kinase inhibits proliferation of the gastric cancer cell line BGC-823. Mol Med Report. 3:361–366. 2010.PubMed/NCBI
11.	Mensah-Osman E, Zavros Y and Merchant JL: Somatostatin stimulates menin gene expression by inhibiting protein kinase A. Am J Physiol Gastrointest Liver Physiol. 295:G843–G854. 2008. View Article : Google Scholar : PubMed/NCBI
12.	Sowa H, Kaji H, Hendy GN, et al: Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem. 279:40267–40275. 2004. View Article : Google Scholar
13.	Kim YS, Burns AL, Goldsmith PK, et al: Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene. 18:5936–5942. 1999. View Article : Google Scholar : PubMed/NCBI
14.	La P, Yang Y, Karnik SK, et al: Menin-mediated caspase 8 expression in suppressing multiple endocrine neoplasia type 1. J Biol Chem. 282:31332–31340. 2007. View Article : Google Scholar : PubMed/NCBI
15.	Guru SC, Crabtree JS, Brown KD, et al: Isolation, genomic organization, and expression analysis of Men1, the murine homolog of the MEN1 gene. Mamm Genome. 10:592–596. 1999. View Article : Google Scholar : PubMed/NCBI
16.	Zhang H, Li W, Wang Q, et al: Glucose-mediated repression of menin promotes pancreatic β-cell proliferation. Endocrinology. 153:602–611. 2012.PubMed/NCBI
17.	Francis J, Lin W, Rozenblatt-Rosen O and Meyerson M: The menin tumor suppressor protein is phosphorylated in response to DNA damage. PLoS One. 6:e161192011. View Article : Google Scholar : PubMed/NCBI
18.	La P, Desmond A, Hou Z, Silva AC, Schnepp RW and Hua X: Tumor suppressor menin: the essential role of nuclear localization signal domains in coordinating gene expression. Oncogene. 25:3537–3546. 2006. View Article : Google Scholar : PubMed/NCBI
19.	Komeili A and O’Shea EK: New perspectives on nuclear transport. Annu Rev Genet. 35:341–364. 2001. View Article : Google Scholar
20.	La P, Silva AC, Hou Z, et al: Direct binding of DNA by tumor suppressor menin. J Biol Chem. 279:49045–49054. 2004. View Article : Google Scholar : PubMed/NCBI
21.	Tell G, Damante G, Caldwell D and Kelley MR: The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal. 7:367–384. 2005. View Article : Google Scholar : PubMed/NCBI
22.	Li Y, Chen Y, Tao Y, Xu J and Chen M: RhoA protein is generally distributed in the nuclei of cancer cells. Oncol Rep. 24:1005–1009. 2010.PubMed/NCBI