Gene Expression in RET/PTC3 and E7 Transgenic Mouse Thyroids: RET/PTC3 But Not E7 Tumors Are Partial and Transient Models of Human Papillary Thyroid Cancers

Burniat, Agnès; Jin, Ling; Detours, Vincent; Driessens, Natacha; Goffard, Jean-Christophe; Santoro, Massimo; Rothstein, Jay L.; Dumont, Jacques Emile; Miot, Françoise; Corvilain, Bernard

doi:10.1210/en.2008-0531

Cited by 23 publications

(16 citation statements)

References 35 publications

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“…On comparing the genetic profiles by microarray analysis of these murine tumors to human PTC, the similarities were most congruent when using mouse PTC tumors at a young age (i.e., 2 months) (50). In particular, mouse and human PTCs had similar patterns of overexpression of genes involved in cell cycle, DNA repair, and genes associated with the immune response (50). As proof-ofconcept that these mice are a model for human PTC, both also had similar patterns of expression for proteins involved in the MAPK pathway.…”

Section: Ret=ptc Mutationsmentioning

confidence: 78%

Lessons from Mouse Models of Thyroid Cancer

Kim

Zhu

2009

Thyroid

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Background: Thyroid cancer is the most common endocrine tumor and is increasing in incidence. The aim of this study was to review mouse models of differentiated thyroid cancer and how they elucidate human thyroid cancer biology. Summary: Differentiated thyroid cancer, primarily papillary and follicular, comprises the majority of thyroid cancers. There has been tremendous growth in the cross-talk between basic science and clinical practice for thyroid cancer management. Insight into the framework of genes responsible for differentiated thyroid cancer has been gained through the use of mouse models. Common genetic alterations found in human papillary thyroid cancer such as RET=PTC rearrangements or the BRAF V600E mutation have genetically modified mouse counterparts. These and other preclinical mouse models have validated the importance of the cyclic adenosine monophosphate (cAMP)=protein kinase A and mitogen-activated protein kinase (MAPK) signaling pathways in papillary thyroid cancer (PTC). RAS mutations have a role in both papillary and follicular thyroid cancer development. Mice with overactivation of the phosphatidylinol-3-kinase (PI3K)-AKT and=or thyrotropinregulated signaling pathways have been found to develop follicular thyroid cancer. Additional mouse models of thyroid cancer that utilize inducible expression systems are in development or are being characterized and will better reflect the majority of human thyroid cancers which are non-hereditary. Advances in in vivo imaging of mice allow for earlier detection of metastasis and the ability to follow tumor growth or regression which may be used in evaluation of pharmaceutical agents. Conclusions: Mouse models have expanded our understanding of the altered signaling pathways that contribute to thyroid cancer tumorigenesis and provide a powerful tool to develop novel diagnostic approaches and therapies.

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Section: Ret=ptc Mutationsmentioning

confidence: 78%

Lessons from Mouse Models of Thyroid Cancer

Kim

Zhu

2009

Thyroid

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“…Gene expression study by microarray technology has shown that important biological processes are differently regulated in the two tumour models: in E7 thyroid cells overexpression of cell cycle genes constitutes the most upregulated process whereas RET PTC3 thyroid cells present an upregulation of human PTC markers, of EGF-like growth factors, and extracellular remodeling genes (Burniat et al, 2008). Similarities with human PTC are observed at a young age but are incomplete.…”

Section: Discussionmentioning

confidence: 99%

“…RET/PTC3 and E7 transgenic mice provided by Dr M Santoro (Napoli) and Dr C Ledent (our Institute) respectively were crossed with wild type C57Bl/6. Both strain progenies were genotyped by PCR (Burniat et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…The transcriptome study (Burniat et al, 2008) revealed differences of gene expression between E7 and RETPTC3 models and between different phases in the evolution of the tumour. The pathological and immunohistological study presented here, in which thyroid function, proliferation, and the two involved signalling pathways were completely tested and they explain the gene expression results.…”

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confidence: 99%

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Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

et al. 2008

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Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2-to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

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“…It is highly expressed in human and mouse thyroids [5,6]. In fact, pendrin mRNA is one of five most abundant transcripts coding for transmembrane proteins expressed in the human thyroid.…”

Section: Arguments For a Role Of Pendrin In Thyroid Physiologymentioning

confidence: 99%

Pendrin: the Thyrocyte Apical Membrane Iodide Transporter?

Twyffels¹,

Massart

Golstein³

et al. 2011

Cell Physiol Biochem

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In the thyroid, the transport of iodide from the extracellular space to the follicular lumen requires two steps: the transport in the cell at the basal side and in the lumen at the apical side. The first step is mediated by the Na⁺/I^- symporter (NIS). In most reviews and textbooks, the second step is presented as mediated by pendrin. In this review, we analyze this assumption. There are several arguments supporting the concept that indeed pendrin plays an important role in thyroid physiology. However, biochemical, clinical and histological data on the thyroid of a patient with Pendred syndrome do not suggest an essential role in iodide transport, which is corroborated by the lack of a thyroid phenotype in pendrin knockout mice. Experiments in vivo and in vitro on polarized and unpolarized cells show that iodide is transported transport of iodide at the apex of the thyroid cell. Moreover, ectopic expression of pendrin in transfected non-thyroid cells is capable of mediating iodide efflux. It is concluded that pendrin may participate in the iodide efflux into thyroid lumen but not as the unique transporter. Moreover, another role of pendrin in mediating Cl^-/HCO₃^- exchange and controlling luminal pH is suggested.

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Gene Expression in RET/PTC3 and E7 Transgenic Mouse Thyroids: RET/PTC3 But Not E7 Tumors Are Partial and Transient Models of Human Papillary Thyroid Cancers

Cited by 23 publications

References 35 publications

Lessons from Mouse Models of Thyroid Cancer

Lessons from Mouse Models of Thyroid Cancer

Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

Pendrin: the Thyrocyte Apical Membrane Iodide Transporter?

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