CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by De Vita, G.
Right arrow Articles by Santoro, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Vita, G.
Right arrow Articles by Santoro, M.

Cell Growth & Differentiation, Vol 9, Issue 1 97-103, Copyright © 1998 by American Association of Cancer Research


ARTICLES

Expression of the RET/PTC1 oncogene impairs the activity of TTF-1 and Pax-8 thyroid transcription factors

G De Vita, M Zannini, AM Cirafici, RM Melillo, R Di Lauro, A Fusco and M Santoro
Dipartimento de Biologia e Patologia Cellulare e Molecolare, Facolta di Medicina e Chirurgia, Universita di Napoli Federico II, Naples, Italy.

The most frequent genetic alterations described thus far in human papillary thyroid carcinomas are somatic rearrangements of the RET proto-oncogene, which generate the chimeric RET/PTC oncogenes. We recently found that the expression of the RET/PTC1 oncogene blocked the expression of the thyroid-differentiated phenotype in rat thyroid epithelial cell line PC CI 3 (PC). Here, we show that this block occurs at a transcriptional level; indeed, the thyroid-specific thyroglobulin and thyroperoxidase gene promoters were inactive in PC-PTC cells. Specific transcription factors, namely, TTF-1 and Pax-8, regulate the expression of differentiated functions in thyroid cells. Here, we show that Pax-8 is expressed at reduced levels in PC-PTC cells and that its adoptive overexpression is unable to restore the activity of target promoters. In contrast, TTF-1 expression is unaltered in PC-PTC cells; however, by using a synthetic promoter that contains its specific target sequence, we demonstrate that TTF-1 is inactive in PC-PTC cells. We conclude that the RET/PTC1 oncogene alters the expression of the thyroid-differentiated phenotype by at least two different mechanisms, ie., down-regulation of Pax-8 protein and mRNA expression and impaired function of TTF-1 and Pax-8, which occurs at a posttranslational level.


This article has been cited by other articles:


Home page
Endocr Relat CancerHome page
T. Endo and T. Kobayashi
Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to thyrocytes
Endocr. Relat. Cancer, October 14, 2013; 20(6): 767 - 776.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. Cras, B. Politis, N. Balitrand, D. Darsin-Bettinger, P. Y. Boelle, B. Cassinat, M.-E. Toubert, and C. Chomienne
Bexarotene via CBP/p300 Induces Suppression of NF-{kappa}B-Dependent Cell Growth and Invasion in Thyroid Cancer
Clin. Cancer Res., January 15, 2012; 18(2): 442 - 453.
[Abstract] [Full Text] [PDF]


Home page
Eur J EndocrinolHome page
H. Hoftijzer, K. A Heemstra, H. Morreau, M. P Stokkel, E. P Corssmit, H. Gelderblom, K. Weijers, A. M Pereira, M. Huijberts, E. Kapiteijn, et al.
Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma
Eur. J. Endocrinol., December 1, 2009; 161(6): 923 - 931.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
S. Durand, C. Ferraro-Peyret, M. Joufre, A. Chave, F. Borson-Chazot, S. Selmi-Ruby, and B. Rousset
Molecular characteristics of papillary thyroid carcinomas without BRAF mutation or RET/PTC rearrangement: relationship with clinico-pathological features
Endocr. Relat. Cancer, June 1, 2009; 16(2): 467 - 481.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
C. Romei, R. Ciampi, P. Faviana, L. Agate, E. Molinaro, V. Bottici, F. Basolo, P. Miccoli, F. Pacini, A. Pinchera, et al.
BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer
Endocr. Relat. Cancer, June 1, 2008; 15(2): 511 - 520.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
T Kogai, K Taki, and G A Brent
Enhancement of sodium/iodide symporter expression in thyroid and breast cancer.
Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
E Puxeddu, J A Knauf, M A Sartor, N Mitsutake, E P Smith, M Medvedovic, C R Tomlinson, S Moretti, and J A Fagin
RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response
Endocr. Relat. Cancer, June 1, 2005; 12(2): 319 - 334.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
N. Mitsutake, J. A. Knauf, S. Mitsutake, C. Mesa Jr., L. Zhang, and J. A. Fagin
Conditional BRAFV600E Expression Induces DNA Synthesis, Apoptosis, Dedifferentiation, and Chromosomal Instability in Thyroid PCCL3 Cells
Cancer Res., March 15, 2005; 65(6): 2465 - 2473.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
D. Vitagliano, F. Carlomagno, M. L. Motti, G. Viglietto, Y. E. Nikiforov, M. N. Nikiforova, J. M. Hershman, A. J. Ryan, A. Fusco, R. M. Melillo, et al.
Regulation of p27Kip1 Protein Levels Contributes to Mitogenic Effects of the RET/PTC Kinase in Thyroid Carcinoma Cells
Cancer Res., June 1, 2004; 64(11): 3823 - 3829.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
T. Di Palma, R. Nitsch, A. Mascia, L. Nitsch, R. Di Lauro, and M. Zannini
The Paired Domain-containing Factor Pax8 and the Homeodomain-containing Factor TTF-1 Directly Interact and Synergistically Activate Transcription
J. Biol. Chem., January 31, 2003; 278(5): 3395 - 3402.
[Abstract] [Full Text] [PDF]


Home page
Ann Clin Lab SciHome page
C. L. Fenton, A. Patel, H. B. Burch, R. M. Tuttle, and G. L. Francis
Nuclear Localization of Thyroid Transcription Factor-1 Correlates with Serum Thyrotropin Activity and May Be Increased in Differentiated Thyroid Carcinomas with Aggressive Clinical Course
Ann. Clin. Lab. Sci., July 1, 2001; 31(3): 245 - 252.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
R. De Leo, S. Miccadei, E. Zammarchi, and D. Civitareale
Role for p300 in Pax 8 Induction of Thyroperoxidase Gene Expression
J. Biol. Chem., November 3, 2000; 275(44): 34100 - 34105.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. Ohno, M. Zannini, O. Levy, N. Carrasco, and R. di Lauro
The Paired-Domain Transcription Factor Pax8 Binds to the Upstream Enhancer of the Rat Sodium/Iodide Symporter Gene and Participates in Both Thyroid-Specific and Cyclic-AMP-Dependent Transcription
Mol. Cell. Biol., March 1, 1999; 19(3): 2051 - 2060.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
R. De Leo, S. Miccadei, E. Zammarchi, and D. Civitareale
Role for p300 in Pax 8 Induction of Thyroperoxidase Gene Expression
J. Biol. Chem., November 3, 2000; 275(44): 34100 - 34105.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1998 by the American Association of Cancer Research.