scholarly journals Loss of Ing3 Expression Results in Growth Retardation and Embryonic Death

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 80
Author(s):  
Dieter Fink ◽  
Tienyin Yau ◽  
Arash Nabbi ◽  
Bettina Wagner ◽  
Christine Wagner ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Cancer Progression ◽  
Growth Retardation ◽  
Developmental Disorders ◽  
Tumour Suppressor ◽  
Neural Tube Closure ◽  
Developmental Defect ◽  
Histone Acetyl Transferase ◽  
Transgenic Mouse Strain ◽  
Candidate Tumour Suppressor

The ING3 candidate tumour suppressor belongs to a family of histone modifying proteins involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair. It is a stoichiometric member of the minimal NuA4 histone acetyl transferase (HAT) complex consisting of EAF6, EPC1, ING3, and TIP60. This complex is responsible for the transcription of an essential cascade of genes involved in embryonic development and in tumour suppression. ING3 has been linked to head and neck and hepatocellular cancers, although its status as a tumour suppressor has not been well established. Recent studies suggest a pro-metastasis role in prostate cancer progression. Here, we describe a transgenic mouse strain with insertional mutation of an UbC-mCherry expression cassette into the endogenous Ing3 locus, resulting in the disruption of ING3 protein expression. Homozygous mutants are embryonically lethal, display growth retardation, and severe developmental disorders. At embryonic day (E) 10.5, the last time point viable homozygous embryos were found, they were approximately half the size of heterozygous mice that develop normally. µCT analysis revealed a developmental defect in neural tube closure, resulting in the failure of formation of closed primary brain vesicles in homozygous mid-gestation embryos. This is consistent with high ING3 expression levels in the embryonic brains of heterozygous and wild type mice and its lack in homozygous mutant embryos that show a lack of ectodermal differentiation. Our data provide direct evidence that ING3 is an essential factor for normal embryonic development and that it plays a fundamental role in prenatal brain formation.

scholarly journals The imbalance of metal-containing proteins and free metal ions in the amniotic fluid during fetal growth

2016 ◽  
Vol 62 (1) ◽  
pp. 69-72 ◽  
Author(s):  
T.N. Pogorelova ◽  
V.A. Linde ◽  
V.O. Gunko ◽  
S.N. Selyutina
Keyword(s):  
Amniotic Fluid ◽  
Metal Ions ◽  
Fetal Growth ◽  
Growth Retardation ◽  
Copper Content ◽  
Developmental Disorders ◽  
Normal Pregnancy ◽  
Fetal Growth Retardation ◽  
Magnesium Ions ◽  
Free Metal

The levels of zinc, copper, iron, and magnesium ions, and some of their binding proteins have been investigated in an amniotic fluid under the fetal growth retardation (FGR). FGR, developed under conditions of placental insufficiency, is characterized by a decrease in the content of zinc, iron, and magnesium ions and by an increase in the copper content in the amniotic fluid in the II and III trimesters of pregnancy. During these trimesters the levels of ceruloplasmin, ferritin, and Ca2+,Mg2+-ATPase were lower in FGR, while the level of zinc-a-2-glycoprotein was higher than during the same periods of normal pregnancy. Changes in the parameters studied in the amniotic fluid were associated with developmental disorders of the newborns. These changes obviously have a pathogenetic importance in the development of FGR, and the levels of metal ions and their ratio in the amniotic fluid can be used as markers of the pre- and postnatal pathology.

Constitutional de novo deletion CNV encompassing REST predisposes to diffuse hyperplastic perilobar nephroblastomatosis (HPLN)

2020 ◽  
pp. jmedgenet-2020-107087
Author(s):  
Zerin Hyder ◽  
Adele Fairclough ◽  
Mike Groom ◽  
Joan Getty ◽  
Elizabeth Alexander ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Cancer Predisposition ◽  
Tumour Suppressor ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Predisposition Genes ◽  
Work Up

BackgroundNephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT.Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex.ObjectiveTo highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN).Methods/resultsArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330–57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042–57,802,010.ConclusionThis delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.

scholarly journals Long-Pentraxin 3 Affects Primary Cilium in Zebrafish Embryo and Cancer Cells via the FGF System

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1756
Author(s):  
Jessica Guerra ◽  
Paola Chiodelli ◽  
Chiara Tobia ◽  
Claudia Gerri ◽  
Marco Presta
Keyword(s):  
Embryonic Development ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Primary Cilium ◽  
Zebrafish Embryo ◽  
Dependent Manner ◽  
Pentraxin 3 ◽  
Left Right Asymmetry ◽  
The Impact ◽  
Cilium Length

Primary cilium drives the left-right asymmetry process during embryonic development. Moreover, its dysregulation contributes to cancer progression by affecting various signaling pathways. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system modulates primary cilium length and plays a pivotal role in embryogenesis and tumor growth. Here, we investigated the impact of the natural FGF trap long-pentraxin 3 (PTX3) on the determination of primary cilium extension in zebrafish embryo and cancer cells. The results demonstrate that down modulation of the PTX3 orthologue ptx3b causes the shortening of primary cilium in zebrafish embryo in a FGF-dependent manner, leading to defects in the left-right asymmetry determination. Conversely, PTX3 upregulation causes the elongation of primary cilium in FGF-dependent cancer cells. Previous observations have identified the PTX3-derived small molecule NSC12 as an orally available FGF trap with anticancer effects on FGF-dependent tumors. In keeping with the non-redundant role of the FGF/FGR system in primary cilium length determination, NSC12 induces the elongation of primary cilium in FGF-dependent tumor cells, thus acting as a ciliogenic anticancer molecule in vitro and in vivo. Together, these findings demonstrate the ability of the natural FGF trap PTX3 to exert a modulatory effect on primary cilium in embryonic development and cancer. Moreover, they set the basis for the design of novel ciliogenic drugs with potential implications for the therapy of FGF-dependent tumors.

scholarly journals The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Praachi B. Jain ◽  
Patrícia S. Guerreiro ◽  
Sara Canato ◽  
Florence Janody
Keyword(s):  
Breast Cancer ◽  
Breast Tumour ◽  
Tissue Growth ◽  
Tumour Suppressor ◽  
Aberrant Expression ◽  
Breast Epithelial Cells ◽  
Mcf10a Cells ◽  
Resistance To Doxorubicin ◽  
Candidate Tumour Suppressor

AbstractAberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.

scholarly journals Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma

2016 ◽  
Vol 12 (5) ◽  
pp. 3305-3311 ◽  
Author(s):  
Giedrius Steponaitis ◽  
Arunas Kazlauskas ◽  
Daina Skiriute ◽  
Indre Valiulyte ◽  
Kestutis Skauminas ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Tumour Suppressor ◽  
Human Astrocytoma ◽  
Candidate Tumour Suppressor

scholarly journals RBM5/LUCA-15 — Tumour Suppression by Control of Apoptosis and the Cell Cycle?

2002 ◽  
Vol 2 ◽  
pp. 1885-1890 ◽  
Author(s):  
Mirna Mourtada-Maarabouni ◽  
Gwyn T. Williams
Keyword(s):  
Gene Locus ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Suppressor Activity ◽  
Tumour Suppression ◽  
Major Significance ◽  
Tumour Suppressor Activity ◽  
Alternatively Spliced ◽  
Candidate Tumour Suppressor

The candidate tumour suppressor gene, LUCA-15, maps to the lung cancer tumour suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four alternatively spliced transcripts, which have been shown to function as regulators of apoptosis, a fact that may have a major significance in tumour regulation. This review highlights evidence that implicates the LUCA-15 locus in the control of apoptosis and cell proliferation, and reports observations that significantly strengthen the case for tumour suppressor activity by this gene.

scholarly journals Frequent silencing of protocadherin 17 , a candidate tumour suppressor for esophageal squamous cell carcinoma

2010 ◽  
Vol 31 (6) ◽  
pp. 1027-1036 ◽  
Author(s):  
Shigeo Haruki ◽  
Issei Imoto ◽  
Ken-ichi Kozaki ◽  
Takeshi Matsui ◽  
Hiroshi Kawachi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Suppressor ◽  
Candidate Tumour Suppressor
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