help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Zeiger, M. A.
Right arrow Articles by Levine, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zeiger, M. A.
Right arrow Articles by Levine, M. A.
Endocrinology Vol. 138, No. 8 3133-3140
Copyright © 1997 by The Endocrine Society

ARTICLES

Thyroid-Specific Expression of Cholera Toxin A1 Subunit Causes Thyroid Hyperplasia and Hyperthyroidism in Transgenic Mice1

Martha A. Zeiger2, Motoyasu Saji2, Yuriy Gusev, William H. Westra, Yumi Takiyama, William C. Dooley, Leonard D. Kohn and Michael A. Levine

Departments of Surgery (M.A.Z., M.S., Y.G., Y.T., W.C.D.), Pathology (W.H.W.), and Medicine (M.A.L.), Johns Hopkins Medical Institutions, Baltimore, Maryland 21205; National Institute of Diabetes, Digestive, and Kidney Diseases (L.D.K.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Martha A. Zeiger, M.D., F.A.C.S., 600 North Wolfe Street, Carnegie 681, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-8611.

Thyroid cell growth and function are regulated by hormones and growth factors binding to cell surface receptors that are coupled via G proteins, Gs and Gq, to the adenylyl cyclase and phospholipase C signal transduction systems, respectively. Activating mutations of the TSH receptor and G{alpha}s have been documented in subsets of thyroid neoplasms. To test the oncogenic potential of activated G{alpha}s in transgenic mice, we used the cholera toxin A1 subunit that constitutively activates G{alpha}s and used the rat thyroglobulin gene promoter for targeting this transgene (TGCT) to thyroid follicular cells. Three (M1392, F1358, and F1286) of six founders identified were able to transmit the transgene to their offspring and thyroid glands from these mice contained elevated levels of cAMP. Concentrations of serum thyroxine were elevated as early as 2 months of age (M 1392 and F 1286). F1358 mice were euthyroid until 8 months of age, at which time they developed hyperthyroidism. All three TGCT lines developed thyroid hyperplasia independent of their thyroxine levels. DNA image analysis of thyroid follicular cells from both the hyper and euthyroid mice showed that DNA index and "S+G2/M" phase were increased compared with normal, changes similar to that seen in poor prognosis human carcinomas. These data suggest that the G{alpha}s-adenylyl cyclase-cAMP pathway has an important role in thyroid hyperplasia and the transgenic mouse models reported herein will allow further examination of the role of this pathway in thyroid oncogenesis.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
N. Yeager, A. Klein-Szanto, S. Kimura, and A. Di Cristofano
Pten Loss in the Mouse Thyroid Causes Goiter and Follicular Adenomas: Insights into Thyroid Function and Cowden Disease Pathogenesis
Cancer Res., February 1, 2007; 67(3): 959 - 966.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
N. Wettschureck and S. Offermanns
Mammalian G Proteins and Their Cell Type Specific Functions
Physiol Rev, October 1, 2005; 85(4): 1159 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
K. Krohn, D. Fuhrer, Y. Bayer, M. Eszlinger, V. Brauer, S. Neumann, and R. Paschke
Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter
Endocr. Rev., June 1, 2005; 26(4): 504 - 524.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. E. Macdonald, K. E. Wortley, L. C. Gowen, K. D. Anderson, J. D. Murray, W. T. Poueymirou, M. V. Simmons, D. Barber, D. M. Valenzuela, A. N. Economides, et al.
Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5
PNAS, February 15, 2005; 102(7): 2496 - 2501.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Ribeiro-Neto, A. Leon, J. Urbani-Brocard, L. Lou, A. Nyska, and D. L. Altschuler
cAMP-dependent Oncogenic Action of Rap1b in the Thyroid Gland
J. Biol. Chem., November 5, 2004; 279(45): 46868 - 46875.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Kato, H. Ying, M. C. Willingham, and S.-Y. Cheng
A Tumor Suppressor Role for Thyroid Hormone {beta} Receptor in a Mouse Model of Thyroid Carcinogenesis
Endocrinology, October 1, 2004; 145(10): 4430 - 4438.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J.-C. Goffard, L. Jin, H. Mircescu, P. Van Hummelen, C. Ledent, J.-E. Dumont, and B. Corvilain
Gene Expression Profile in Thyroid of Transgenic Mice Overexpressing the Adenosine Receptor 2a
Mol. Endocrinol., January 1, 2004; 18(1): 194 - 213.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. T. Collins, N. J. Sarlis, M. J. Merino, J. Monroe, S. E. Crawford, J. A. Krakoff, L. C. Guthrie, S. Bonat, P. G. Robey, and A. Shenker
Thyroid Carcinoma in the McCune-Albright Syndrome: Contributory Role of Activating Gs{alpha} Mutations
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4413 - 4417.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
H. Ying, H. Suzuki, H. Furumoto, R. Walker, P. Meltzer, M. C. Willingham, and S.-Y. Cheng
Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma
Carcinogenesis, September 1, 2003; 24(9): 1467 - 1479.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. A. Fagin
Minireview: Branded from the Start--Distinct Oncogenic Initiating Events May Determine Tumor Fate in the Thyroid
Mol. Endocrinol., May 1, 2002; 16(5): 903 - 911.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Clement, S. Refetoff, B. Robaye, J. E. Dumont, and S. Schurmans
Low TSH Requirement and Goiter in Transgenic Mice Overexpressing IGF-I and IGF-I Receptor in the Thyroid Gland
Endocrinology, December 1, 2001; 142(12): 5131 - 5139.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
T. Kimura, A. Van Keymeulen, J. Golstein, A. Fusco, J. E. Dumont, and P. P. Roger
Regulation of Thyroid Cell Proliferation by TSH and Other Factors: A Critical Evaluation of in Vitro Models
Endocr. Rev., October 1, 2001; 22(5): 631 - 656.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu
Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting
Endocr. Rev., October 1, 2001; 22(5): 675 - 705.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Krohn and R. Paschke
Progress in Understanding the Etiology of Thyroid Autonomy
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3336 - 3345.
[Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. M. Campbell, L. de Lecea, D. M. Severynse, M. G. Caron, M. J. McGrath, S. B. Sparber, L.-Y. Sun, and F. H. Burton
OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons
J. Neurosci., June 15, 1999; 19(12): 5044 - 5053.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Derwahl, M. Broecker, and Z. Kraiem
Thyrotropin May Not Be the Dominant Growth Factor in Benign and Malignant Thyroid Tumors
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 829 - 834.
[Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. D. Ringel, M. Saji, W. F. Schwindinger, D. Segev, M. A. Zeiger, and M. A. Levine
Absence of Activating Mutations of the Genes Encoding the {alpha}-Subunits of G11 and Gq in Thyroid Neoplasia
J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 554 - 559.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society