help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on June 20, 2003
Molecular Endocrinology, doi:10.1210/me.2003-0154
Molecular Endocrinology Vol. 0, No. 2003 200301541-
doi:10.1210/me.2003-0154
Copyright © 2003 by the Endocrine Society.
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
17/9/1880    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bertolino, P.
Right arrow Articles by Zhang, C.-X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bertolino, P.
Right arrow Articles by Zhang, C.-X.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene

Submitted on April 23, 2003
Accepted on June 9, 2003

Heterozygous Men1 Mutant Mice Develop a Range of Endocrine Tumors Mimicking Multiple Endocrine Neoplasia Type 1

Philippe Bertolino1, Wei-Min Tong1, Dominique Galendo1, Zhao-Qi Wang1*, and Chang-Xian Zhang1

1 Laboratory of Genetics, CNRS, UMR5641, Faculty of Medicine University of Lyon 1, 8 Avenue Rockefeller, 69373 Lyon, France; International Agency for Research on Cancer (IARC), 150 cours Albert-Thomas, 69008 Lyon, France

* To whom correspondence should be addressed. E-mail: zqwang{at}iarc.fr.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by the occurrence of multiple endocrine tumors of the parathyroid, pancreas and anterior pituitary in patients. To study tumorigenesis related to the MEN1 syndrome, we have generated Men1 knockout mice using the gene targeting approach. Heterozygous Men1 mutant mice developed the same range of major endocrine tumors as is seen in MEN1 patients, affecting the parathyroid, pancreatic islets, pituitary and adrenal glands, as well as the thyroid, and exhibiting multistage tumor progression with metastatic potential. In particular, extra-pancreatic gastrinoma, pancreatic glucagonoma, and mixed hormone-producingtumors in islets were observed. In addition, there was a high incidence of gonadal tumors of endocrine origin, i.e. Leydig cell tumors, and ovary sex-cord stromal cell tumors in heterozygous Men1 mutant mice. Hormonal disturbance, such as abnormal PTH and insulin levels, was also observed in these mice. These tumors were associated with loss of heterozygosity of the wild-type Men1 allele, suggesting that menin is involved in suppressing the development of these endocrine tumors. All these features are reminiscent of MEN1 symptoms in humans and establish heterozygous Men1 mutant mice as a suitable model for this disease.
Key words: Men1 • tumor suppressor • LOH • endocrine tumors • hormone disturbance




This article has been cited by other articles:


Home page
 J EndocrinolHome page
S. Fontaniere, B. Duvillie, R. Scharfmann, C. Carreira, Z.-Q. Wang, and C.-X. Zhang
Tumour suppressor menin is essential for development of the pancreatic endocrine cells
J. Endocrinol., November 1, 2008; 199(2): 287 - 298.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
N. Hussein, J. Lu, H. Casse, S. Fontaniere, A.-M. Morera, S. M. Guittot, A. Calender, N. Di Clemente, and C. X Zhang
Deregulation of anti-Mullerian hormone/BMP and transforming growth factor-{beta} pathways in Leydig cell lesions developed in male heterozygous multiple endocrine neoplasia type 1 mutant mice
Endocr. Relat. Cancer, March 1, 2008; 15(1): 217 - 227.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
H-C J. Shen, J. E Rosen, L. M Yang, S. A Savage, A L. Burns, C. M Mateo, S. K Agarwal, S. C Chandrasekharappa, A. M Spiegel, F. S Collins, et al.
Parathyroid tumor development involves deregulation of homeobox genes
Endocr. Relat. Cancer, March 1, 2008; 15(1): 267 - 275.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Matoso, Z. Zhou, R. Hayama, A. Flesken-Nikitin, and A. Yu. Nikitin
Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia
Carcinogenesis, March 1, 2008; 29(3): 620 - 628.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. La, Y. Yang, S. K. Karnik, A. C. Silva, R. W. Schnepp, S. K. Kim, and X. Hua
Menin-mediated Caspase 8 Expression in Suppressing Multiple Endocrine Neoplasia Type 1
J. Biol. Chem., October 26, 2007; 282(43): 31332 - 31340.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
Y. Ji, N. B. Prasad, E. A. Novotny, S. Kaur, A. Elkahloun, Y. Chen, R.-Z. Zhang, M.-L. Chu, S. K. Agarwal, S. J. Marx, et al.
Mouse Embryo Fibroblasts Lacking the Tumor Suppressor Menin Show Altered Expression of Extracellular Matrix Protein Genes
Mol. Cancer Res., October 1, 2007; 5(10): 1041 - 1051.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X.-H. Pei, F. Bai, M. D. Smith, and Y. Xiong
p18Ink4c Collaborates with Men1 to Constrain Lung Stem Cell Expansion and Suppress Non-Small-Cell Lung Cancers
Cancer Res., April 1, 2007; 67(7): 3162 - 3170.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
F. Bai, X.-H. Pei, T. Nishikawa, M. D. Smith, and Y. Xiong
p18Ink4c, but Not p27Kip1, Collaborates with Men1 To Suppress Neuroendocrine Organ Tumors
Mol. Cell. Biol., February 15, 2007; 27(4): 1495 - 1504.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
S Fontaniere, J Tost, A Wierinckx, J Lachuer, J Lu, N Hussein, F Busato, I Gut, Z-Q Wang, and C-X Zhang
Gene expression profiling in insulinomas of Men1 {beta}-cell mutant mice reveals early genetic and epigenetic events involved in pancreatic {beta}-cell tumorigenesis
Endocr. Relat. Cancer, December 1, 2006; 13(4): 1223 - 1236.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
L. E. MacConaill, C. M. Hughes, O. Rozenblatt-Rosen, S. Nannepaga, and M. Meyerson
Phosphorylation of the Menin Tumor Suppressor Protein on Serine 543 and Serine 583
Mol. Cancer Res., October 1, 2006; 4(10): 793 - 801.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. W. Schnepp, Y.-X. Chen, H. Wang, T. Cash, A. Silva, J. A. Diehl, E. Brown, and X. Hua
Mutation of Tumor Suppressor Gene Men1 Acutely Enhances Proliferation of Pancreatic Islet Cells
Cancer Res., June 1, 2006; 66(11): 5707 - 5715.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
P. Roccabianca, M. Rondena, S. Paltrinieri, V. Pocacqua, P. Scarpa, S. Faverzani, E. Scanziani, and M. Caniatti
Multiple Endocrine Neoplasia Type-I-like Syndrome in Two Cats
Vet. Pathol., May 1, 2006; 43(3): 345 - 352.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Matsumoto, A. Kubo, H. Liu, K. Akita, F. Laub, F. Ramirez, G. Keller, and S. L. Friedman
Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6
Blood, February 15, 2006; 107(4): 1357 - 1365.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
S Corbetta, L Vicentini, S Ferrero, A Lania, G Mantovani, D Cordella, P Beck-Peccoz, and A Spada
Activity and function of the nuclear factor kappaB pathway in human parathyroid tumors
Endocr. Relat. Cancer, December 1, 2005; 12(4): 929 - 937.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. K. Karnik, C. M. Hughes, X. Gu, O. Rozenblatt-Rosen, G. W. McLean, Y. Xiong, M. Meyerson, and S. K. Kim
Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27Kip1 and p18INK4c
PNAS, October 11, 2005; 102(41): 14659 - 14664.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. C. Scacheri, A. L. Kennedy, K. Chin, M. T. Miller, J. G. Hodgson, J. W. Gray, S. J. Marx, A. M. Spiegel, and F. S. Collins
Pancreatic Insulinomas in Multiple Endocrine Neoplasia, Type I Knockout Mice Can Develop in the Absence of Chromosome Instability or Microsatellite Instability
Cancer Res., October 1, 2004; 64(19): 7039 - 7044.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Sowa, H. Kaji, G. N. Hendy, L. Canaff, T. Komori, T. Sugimoto, and K. Chihara
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., September 24, 2004; 279(39): 40267 - 40275.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. W. Schnepp, Z. Hou, H. Wang, C. Petersen, A. Silva, H. Masai, and X. Hua
Functional Interaction between Tumor Suppressor Menin and Activator of S-Phase Kinase
Cancer Res., September 15, 2004; 64(18): 6791 - 6796.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Ratineau, C. Bernard, G. Poncet, M. Blanc, C. Josso, S. Fontaniere, A. Calender, J. A. Chayvialle, C.-X. Zhang, and C. Roche
Reduction of Menin Expression Enhances Cell Proliferation and Is Tumorigenic in Intestinal Epithelial Cells
J. Biol. Chem., June 4, 2004; 279(23): 24477 - 24484.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. Stalberg, P. Grimfjard, M. Santesson, Y. Zhou, D. Lindberg, A. Gobl, K. Oberg, G. Westin, J. Rastad, S. Wang, et al.
Transfection of the Multiple Endocrine Neoplasia Type 1 Gene to a Human Endocrine Pancreatic Tumor Cell Line Inhibits Cell Growth and Affects Expression of JunD, {delta}-Like Protein 1/Preadipocyte Factor-1, Proliferating Cell Nuclear Antigen, and QM/Jif-1
J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2326 - 2337.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. A. Biondi, M. G. Gartside, P. Waring, K. A. Loffler, M. S. Stark, M. A. Magnuson, G. F. Kay, and N. K. Hayward
Conditional Inactivation of the Men1 Gene Leads to Pancreatic and Pituitary Tumorigenesis but Does Not Affect Normal Development of These Tissues
Mol. Cell. Biol., April 15, 2004; 24(8): 3125 - 3131.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Sowa, H. Kaji, R. Kitazawa, S. Kitazawa, T. Tsukamoto, S. Yano, T. Tsukada, L. Canaff, G. N. Hendy, T. Sugimoto, et al.
Menin Inactivation Leads to Loss of Transforming Growth Factor {beta} Inhibition of Parathyroid Cell Proliferation and Parathyroid Hormone Secretion
Cancer Res., March 15, 2004; 64(6): 2222 - 2228.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. K. Libutti, J. S. Crabtree, D. Lorang, A. L. Burns, C. Mazzanti, S. M. Hewitt, S. O'Connor, J. M. Ward, M. R. Emmert-Buck, A. Remaley, et al.
Parathyroid Gland-specific Deletion of the Mouse Men1 Gene Results in Parathyroid Neoplasia and Hypercalcemic Hyperparathyroidism
Cancer Res., November 15, 2003; 63(22): 8022 - 8028.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2003 by The Endocrine Society