help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watanabe, T.
Right arrow Articles by Takahashi, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, T.
Right arrow Articles by Takahashi, M.
(American Journal of Pathology. 2002;161:249-256.)
© 2002 American Society for Investigative Pathology

Regular Articles

Characterization of Gene Expression Induced by RET with MEN2A or MEN2B Mutation

Tsuyoshi Watanabe*{dagger}, Masatoshi Ichihara*, Mizuo Hashimoto*, Keiko Shimono{dagger}, Yoshie Shimoyama*, Tetsuro Nagasaka{ddagger}, Yoshiki Murakumo*, Hideki Murakami*, Hideshi Sugiura{dagger}, Hisashi Iwata{dagger}, Naoki Ishiguro{dagger} and Masahide Takahashi*

From the Departments of Pathology,*Orthopedic Surgery,{dagger}and Laboratory Medicine,{ddagger}Nagoya University Graduate School of Medicine, Nagoya, Japan

Germ-line point mutations of the RET gene are responsible for multiple endocrine neoplasia (MEN) type 2A and 2B that develop medullary thyroid carcinoma and pheochromocytoma. We performed a differential display analysis of gene expression using NIH 3T3 cells expressing the RET-MEN2A or RET-MEN2B mutant proteins. As a consequence, we identified 10 genes induced by both mutant proteins and eight genes repressed by them. The inducible genes include cyclin D1, cathepsins B and L, and cofilin genes that are known to be involved in cell growth, tumor progression, and invasion. In contrast, the repressed genes include type I collagen, lysyl oxidase, annexin I, and tissue inhibitor of matrix metalloproteinase 3 (TIMP3) genes that have been implicated in tumor suppression. In addition, six RET-MEN2A- and five RET-MEN2B-inducible genes were identified. Among 21 genes induced by RET-MEN2A and/or RET-MEN2B, six genes including cyclin D1, cathepsin B, cofilin, ring finger protein 11 (RNF11), integrin-{alpha}6, and stanniocalcin 1 (STC1) genes were also induced in TGW human neuroblastoma cells in response to glial cell line-derived neurotrophic factor stimulation. Because the STC1 gene was found to be highly induced by both RET-MEN2B and glial cell line-derived neurotrophic factor stimulation, and the expression of its product was detected in medullary thyroid carcinoma with the MEN2B mutation by immunohistochemistry, this may suggest a possible role for STC1 in the development of MEN 2B phenotype.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
T. S. Gujral, W. van Veelen, D. S. Richardson, S. M. Myers, J. A. Meens, D. S. Acton, M. Dunach, B. E. Elliott, J. W.M. Hoppener, and L. M. Mulligan
A Novel RET Kinase-{beta}-Catenin Signaling Pathway Contributes to Tumorigenesis in Thyroid Carcinoma
Cancer Res., March 1, 2008; 68(5): 1338 - 1346.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
C. J. Wray, T. A. Rich, S. G. Waguespack, J. E. Lee, N. D. Perrier, and D. B. Evans
Failure to Recognize Multiple Endocrine Neoplasia 2B: More Common Than We Think?
Ann. Surg. Oncol., January 1, 2008; 15(1): 293 - 301.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. J. Pollard, M. El-Bahrawy, R. Poulsom, G. Elia, P. Killick, G. Kelly, T. Hunt, R. Jeffery, P. Seedhar, J. Barwell, et al.
Expression of HIF-1{alpha}, HIF-2{alpha} (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4593 - 4598.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. W. B. de Groot, T. P. Links, J. T. M. Plukker, C. J. M. Lips, and R. M. W. Hofstra
RET as a Diagnostic and Therapeutic Target in Sporadic and Hereditary Endocrine Tumors
Endocr. Rev., August 1, 2006; 27(5): 535 - 560.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Y. Yeung, K. P. Lai, H. Y. Chan, N. K. Mak, G. F. Wagner, and C. K. C. Wong
Hypoxia-Inducible Factor-1-Mediated Activation of Stanniocalcin-1 in Human Cancer Cells
Endocrinology, November 1, 2005; 146(11): 4951 - 4960.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. Drosten, G. Hilken, M. Bockmann, F. Rodicker, N. Mise, A. N. Cranston, U. Dahmen, B. A. J. Ponder, and B. M. Putzer
Role of MEN2A-Derived RET in Maintenance and Proliferation of Medullary Thyroid Carcinoma
J Natl Cancer Inst, August 18, 2004; 96(16): 1231 - 1239.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. M. Myers and L. M. Mulligan
The RET Receptor Is Linked to Stress Response Pathways
Cancer Res., July 1, 2004; 64(13): 4453 - 4463.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Jain, M. A. Watson, M. K. DeBenedetti, Y. Hiraki, J. F. Moley, and J. Milbrandt
Expression Profiles Provide Insights into Early Malignant Potential and Skeletal Abnormalities in Multiple Endocrine Neoplasia Type 2B Syndrome Tumors
Cancer Res., June 1, 2004; 64(11): 3907 - 3913.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Fukuda, M. Ichihara, T. Morinaga, K. Kawai, H. Hayashi, Y. Murakumo, S. Matsuo, and M. Takahashi
Identification of a Novel Glial Cell Line-derived Neurotrophic Factor-inducible Gene Required for Renal Branching Morphogenesis
J. Biol. Chem., December 12, 2003; 278(50): 50386 - 50392.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.