Identification of Differentially Expressed Genes in Papillary Thyroid Carcinomas With and Without Rearrangements of the Tyrosine Kinase Receptors RET and/or NTRK1

Musholt, Thomas J.; Brehm, Christoph; Hanack, Julia; Wasielewski, Reinhard von; Musholt, Petra B.

doi:10.1016/j.jss.2005.08.013

Cited by 20 publications

(12 citation statements)

References 44 publications

(36 reference statements)

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“…Upregulation of 14-3-3β promoted cell proliferation and tumor formation by the mitogen-activated protein kinase (MAPK)-dependent signaling pathway in NIH3T3 cells (39). Increased expression of 14-3-3β was observed in Kaposi's sarcoma and papillary thyroid carcinomas and promoted cell proliferation and tumor progression (41,42). Our previous studies demonstrated that 14-3-3β expression increased with the degree of human astrocytoma.…”

Section: Discussionmentioning

confidence: 97%

14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

Gong

Wang

et al. 2013

Oncology Reports

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Abstract. We previously demonstrated that 14-3-3β is overexpressed in astrocytomas; however, the underlying mechanisms are poorly understood. Based on the reported multiple functions of 14-3-3β, we hypothesized that it interacts with glycogen synthase kinase 3 β (GSK3β), which regulates β-catenin-mediated oncogene expression and contributes to tumorigenesis and astrocytoma progression. To test these hypotheses, we used 14-3-3β overexpression vectors and small interfering RNA (siRNA) transfection in the human normal astrocyte cell line SVGp12 and the glioma cell line U87, respectively. The results showed that overexpression of 14-3-3β promoted the proliferation of SVGp12 cells, while knockdown of 14-3-3β inhibited the proliferation of U87 cells as analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) assays. In Flag-tagged 14-3-3β-overexpressing cells, GSK3β was co-immunoprecipitated with 14-3-3β using a Flag antibody. Knockdown of β-catenin by siRNA blocked cell proliferation induced by overexpression of 14-3-3β. Furthermore, overexpression of 14-3-3β suppressed the phosphorylation of β-catenin leading to its accumulation and nuclear translocation as revealed by western blot analysis. In addition, β-catenin nuclear translocation induced by overexpression of 14-3-3β activated the transcription of oncogenes including c-myc and cyclin D1. Collectively, these results revealed that 14-3-3β regulates the proliferation of astrocytes and glioma cells through the GSK3β/β-catenin signaling pathway. The delineated mechanism of 14-3-3β may be responsible for the tumorigenesis and progression of human astrocytomas. Thus, new therapeutic strategies or drugs aimed at 14-3-3β may have potential for the treatment of human astrocytomas. IntroductionThe highly conserved family of 14-3-3 proteins consisting of seven isoforms (β, γ, ε, η, θ, σ and ξ) has been demonstrated to bind to a wide variety of proteins and to play important roles in a variety of biological processes, including cell cycle control, cell survival and cell death through various signal transduction pathways (1-4). In normal or tumor cells and tissues, 14-3-3 proteins have been suggested to participate in a broad spectrum of human diseases such as cancer (5). However, 14-3-3 proteins exhibit isoform-specific expression in different types of cells and tissues, and the function of 14-3-3 proteins is complex and intricate owing to the high sequence homology of its isoforms (6).The role of 14-3-3 proteins in carcinogenesis has been extensively studied. Accumulating evidence has established an association between 14-3-3 proteins and many types of cancers, including lung, breast, neck and head cancers (5,7). However, different isoforms may act as oncogenes or tumor suppressors in different types of cancers. Abundant expression of 14-3-3ξ is found in breast cancers and promotes cancer progression via the PI3K/Akt pathway (8,9). Knockdown of 14-3-3ξ was found to significantly inhibit lung cancer cell proliferation a...

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Section: Discussionmentioning

confidence: 97%

14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

Gong

Wang

et al. 2013

Oncology Reports

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“…However, as majority of these transcripts have unknown protein expression in human thyroid tissue (83/130) and unknown gene expression in mouse thyroid tissue (96/130) (according to The Human Protein Atlas and UniGene, respectively), the possibility to determine this distribution is limited. Furthermore, not corresponding with UniGene and The Human Protein Atlas, Dmbt1 (synonym: Crp ) and Rab27a are expressed at the mRNA level in mouse thyroid and at the protein level in human thyroid, respectively [33,34]. In addition, Dnase1 has detectable mRNA levels in mouse thyroid [29].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

et al. 2012

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BackgroundAstatine-211 (211At) is an alpha particle emitting halogen with almost optimal linear energy transfer for creating DNA double-strand breaks and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Unbound 211At accumulates in the thyroid gland, and the concept of basal radiation-induced biological effects in the thyroid tissue is, to a high degree, unknown and is most valuable.MethodsFemale BALB/c nude mice were intravenously injected with 0.064 to 42 kBq of 211At, resulting in absorbed doses of 0.05 to 32 Gy in the thyroid gland. Thyroids were removed 24 h after injection; total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips.ResultsThyroids exposed to 211At revealed distinctive gene expression profiles compared to non-irradiated controls. A larger number of genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and higher absorbed doses (11 and 32 Gy). The proportion of dose-specific genes increased with decreased absorbed dose. Additionally, 1.4 Gy often exerted opposite regulation on gene expression compared to the other absorbed doses. Using Gene Ontology data, an immunological effect was detected at 0.05 and 11 Gy. Effects on cellular response to external stress and cell cycle regulation and proliferation were detected at 1.4 and 11 Gy.ConclusionsConclusively, the cellular response to ionizing radiation is complex and differs with absorbed dose. The response acquired at high absorbed doses cannot be extrapolated down to low absorbed doses or vice versa. We also demonstrated that the thyroid - already at absorbed doses similar to those obtained in radionuclide therapy - responds with expression of a high number of genes. Due to the increased heterogeneous irradiation at low absorbed doses, we suggest that this response partly originates from non-irradiated cells in the tissue, i.e., bystander cells.

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“…These marker proteins have included Galectin-3 (Orlandi et al 1998), CD44v6 (Bartolazzi et al 2001, HBME-1 (Miettinen & Karkkainen 1996), CK19 (Schelfhout et al 1989), hTERT (Wood et al 2000a), and S100A4 (Ito et al 2004). The recent availability of microarray techniques has allowed a different approach, through the identification of clusters of genes, whose expression is specific of some types of thyroid tumors and malignancies (Lubitz et al 2005, Musholt et al 2006. Since a consistent series of thyroid malignant tissues display a positive immunostaining for at least one of the p53 family members (Table 1; Frasca et al 2003, Malaguarnera et al 2005, it is reasonable to hypothesize a possible use of these proteins in thyroid nodule differential diagnosis by immunostaining in both tissue specimens and cytoaspirates.…”

Section: Clinical Applications Of P53 Family Member Expression In Thymentioning

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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Identification of Differentially Expressed Genes in Papillary Thyroid Carcinomas With and Without Rearrangements of the Tyrosine Kinase Receptors RET and/or NTRK1

Cited by 20 publications

References 44 publications

14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

14-3-3β regulates the proliferation of glioma cells through the GSK3β/β-catenin signaling pathway

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

p53 family proteins in thyroid cancer

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