Molecular Events in Follicular Thyroid Tumors

Kroll, Todd G.

doi:10.1007/1-4020-8107-3_4

Cited by 42 publications

(26 citation statements)

References 197 publications

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“…Interestingly, these two genetic backgrounds rarely overlap in the same tumor, suggesting that two independent pathways are involved in the development of FTC (Nikiforova et al 2003). While the Ras mutation is not restricted to a particular histological type, PAX8/PPARg rearrangement mainly presents with follicular neoplasms and a small portion of follicular variants of papillary thyroid cancers (Dwight et al 2003, Nikiforova et al 2003, Kroll 2004, Lacroix et al 2004, Koenig 2010, Nikiforov & Nikiforova 2011. Because the expression of PPFP indicates a favorable clinical presentation and prognosis, FTCs presenting with PAX8/PPARg rearrangement are thought to be a less aggressive subtype (Sahin et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Li¹,

Wang²,

Liu³

et al. 2012

Endocrine-Related Cancer

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The fusion gene encoding the thyroid-specific transcription factor PAX8 and peroxisome proliferator-activated receptor g (PPARg (PPARG)) (designated as the PPFP gene) is oncogenic and implicated in the development of follicular thyroid carcinoma (FTC). The effects of PPFP transfection on the biological characteristics of Nthy-ori 3-1 cells were studied by MTT assay, colony formation, soft-agar colony formation, and scratch wound-healing assays as well as by flow cytometry. Furthermore, the differentially expressed proteins were analyzed on 2-DE maps and identified by MALDI-TOF-MS. Validation of five identified proteins (prohibitin, galectin-1, cytokeratin 8 (CK8), CK19, and HSP27) was determined by western blot analysis. PPFP not only significantly increased the viability, proliferation, and mobility of the Nthy-ori 3-1 cells but also markedly inhibited cellular apoptosis. Twenty-eight differentially expressed proteins were identified, among which 19 proteins were upregulated and nine proteins were downregulated in Nthy-ori 3-1 PPFP (Nthy-ori 3-1 cells transfected with PPFP). The western blot results, which were consistent with the proteome analysis results, showed that prohibitin was downregulated, whereas galectin-1, CK8, CK19, and HSP27 were upregulated in Nthy-ori 3-1 PPFP . Our results suggest that PPFP plays an important role in malignant thyroid transformation. Proteomic analysis of the differentially expressed proteins in PPFP-transfected cells provides important information for further study of the carcinogenic mechanism of PPFP in FTCs.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Li¹,

Wang²,

Liu³

et al. 2012

Endocrine-Related Cancer

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“…Over time, these responses form the basis of genetic variability to disease susceptibility. Aberrant changes in linear DNA sequence result in mutations, deletions, gene fusion, tandem duplications, or gene amplifications causing dysregulation of gene expression that underlies the genesis of disease [1][2][3][4][5][6][7]. Recently, however, it has become clear that epigenetic disruption of gene expression plays an equally important role in the development of disease [8][9][10] and, arguably, that this process is more susceptible than the former to environmental modulation.…”

Section: Epigenetics Meets Genetics In Disease Susceptibilitymentioning

confidence: 99%

Epigenetic reprogramming and imprinting in origins of disease

Tang

2007

Rev Endocr Metab Disord

217

134

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The traditional view that gene and environment interactions control disease susceptibility can now be expanded to include epigenetic reprogramming as a key determinant of origins of human disease. Currently, epigenetics is defined as heritable changes in gene expression that do not alter DNA sequence but are mitotically and trans-generationally inheritable. Epigenetic reprogramming is the process by which an organism's genotype interacts with the environment to produce its phenotype and provides a framework for explaining individual variations and the uniqueness of cells, tissues, or organs despite identical genetic information. The main epigenetic mediators are histone modification, DNA methylation, and non-coding RNAs. They regulate crucial cellular functions such as genome stability, X-chromosome inactivation, gene imprinting, and reprogramming of non-imprinting genes, and work on developmental plasticity such that exposures to endogenous or exogenous factors during critical periods permanently alter the structure or function of specific organ systems. Developmental epigenetics is believed to establish "adaptive" phenotypes to meet the demands of the later-life environment. Resulting phenotypes that match predicted later-life demands will promote health, while a high degree of mismatch will impede adaptability to later-life challenges and elevate disease risk. The rapid introduction of synthetic chemicals, medical interventions, environmental pollutants, and lifestyle choices, may result in conflict with the programmed adaptive changes made during early development, and explain the alarming increases in some diseases. The recent identification of a significant number of epigenetically regulated genes in various model systems has prepared the field to take on the challenge of characterizing distinct epigenomes related to various diseases. Improvements in human health could then be redirected from curative care to personalized, preventive medicine based, in part, on epigenetic markings etched in the "margins" of one's genetic make-up. NIH Public Access Author ManuscriptRev Endocr Metab Disord. Author manuscript; available in PMC 2014 June 13. Epigenetics meets genetics in disease susceptibilityIn the past, susceptibility of disease was believed to be determined solely by inheritable information carried on the primary sequence of the DNA. Individuals are endowed with different genotypes that dictate how they respond to endogenous factors such as development cues, hormones, and cytokines or to exogenous influences, including nutrient availability, infection, physical activities, social behavior, and other environmental factors. Over time, these responses form the basis of genetic variability to disease susceptibility. Aberrant changes in linear DNA sequence result in mutations, deletions, gene fusion, tandem duplications, or gene amplifications causing dysregulation of gene expression that underlies the genesis of disease [1][2][3][4][5][6][7]. Recently, however, it has become clear that epigenetic disr...

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“…It mainly includes the aberrant activation of the RAS/RAF/MEK/ERK pathway (Kroll 2004, Hunt 2005. These alterations regard the rearrangements of Ret/PTC and Trk tyrosine kinase receptors and point mutations of RAS or BRAF genes (Kroll 2004, Hunt 2005.…”

Section: P53 In Thyroid Cancermentioning

confidence: 99%

p53 family proteins in thyroid cancer

Malaguarnera¹,

Vella²,

Vigneri³

et al. 2007

Endocr Relat Cancer

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At variance with other human malignancies, p53 mutations are not frequent in thyroid cancer and are believed to be responsible mainly for cancer progression to poorly differentiated and aggressive phenotype. p63 and p73, two proteins with a high degree of homology with p53, are overexpressed in thyroid cancer, but their role in cancer initiation or progression is controversial. Regulation of p53 family protein function depends on: (1) the balance between the expression of transcriptionally active (p53, TAp63, and TAp73) and inactive isoforms (DNp63 and DNp73); (2) their interaction and competition at DNA-responsive elements; (3) their interaction with regulatory proteins, either inhibitory or activating. In thyroid cancer, therefore, although mutations of the p53 oncosuppressor protein family are rare, other mechanisms are present, including aberrant expression of p53 family dominant negative isoforms, up-regulation of inhibitory proteins, and functional inhibition of activating proteins. The overall result is a defective oncosuppressor activity. These inactivating mechanisms may be present in the early stages of thyroid cancer and in different cancer histotypes. A better understanding of this complex network may not only ameliorate our comprehension of cancer biology, but also open the possibility of innovative diagnostic procedures and the development of targeted therapies.

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Molecular Events in Follicular Thyroid Tumors

Cited by 42 publications

References 197 publications

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Epigenetic reprogramming and imprinting in origins of disease

p53 family proteins in thyroid cancer

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