The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Robert I. Richards - One of the best experts on this subject based on the ideXlab platform.
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XML Template (2015) [12.1.2015–12:46pm] [1–7] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/EBMJ/Vol00000/140218/APPFile/SG-EBMJ140218.3d (EBM) [PREPRINTER stage]
2016Co-Authors: Robert I. Richards, Cheng Shoou Lee, A Choo, Sonia DayanAbstract:WWOX, the Chromosomal Fragile Site FRA16D spanning gene: It
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RESEARCH ARTICLE Tumor Suppressor WWOX Contributes to the Elimination of Tumorigenic Cells in Drosophila melanogaster
2016Co-Authors: Louise V. O’keefe, A Choo, Cheng Shoou Lee, Robert I. RichardsAbstract:WWOX is a>1Mb gene spanning FRA16D Common Chromosomal Fragile Site, a region of DNA instability in cancer. Consequently, alteredWWOX levels have been observed in a wide variety of cancers. In vitro studies have identified a large number and variety of poten-tial roles for WWOX. Although its normal role in vivo and functional contribution to cancer have not been fully defined, WWOX does have an integral role in metabolism and can sup-press tumor growth. Using Drosophila melanogaster as an in vivomodel system, we find that WWOX is a modulator of TNFα/Egr-mediated cell death. We found that altered levels of WWOX can modify phenotypes generated by low level ectopic expression of TNFα/Egr and this corresponds to altered levels of Caspase 3 activity. These results demonstrate an in vivo role for WWOX in promoting cell death. This form of cell death is accompanied by an increase in levels of reactive oxygen species, the regulation of which we have previously shown can also be modified by altered WWOX activity. We now hypothesise that, through regulation of reactive oxygen species, WWOX constitutes a link between alterations in cel-lular metabolism observed in cancer cells and their ability to evade normal cell death path-ways. We have further shown that WWOX activity is required for the efficient removal of tumorigenic cells from a developing epithelial tissue. Together these results provide a molecular basis for the tumor suppressor functions of WWOX and the better prognosis observed in cancer patients with higher levels of WWOX activity. Understanding the con-served cellular pathways to which WWOX contributes provides novel possibilities for the development of therapeutic approaches to restore WWOX function in cancer
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WWOX, the Chromosomal Fragile Site FRA16D spanning gene: Its role in metabolism and contribution to cancer:
Experimental biology and medicine (Maywood N.J.), 2015Co-Authors: Robert I. Richards, Sonia Dayan, Amanda Choo, Cheng Shoou Lee, Louise V. O'keefeAbstract:The WWOX gene spans the common Chromosomal Fragile Site FRA16D that is located within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which may contribute to the very low abundance of the full-length 1.4 kb mRNA. Alternative splicing also accounts for a variety of aberrant transcripts, most of which are devoid of C-terminal sequences required for WWOX to act as an oxidoreductase. The mouse WWOX gene also spans a Chromosomal Fragile Site implying some sort of functional relationship that confers a selective advantage. The encoded protein domains of WWOX are conserved through evolution (between humans and Drosophila melanogaster) and include WW domains, an NAD -binding Site, short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization signals. This homology has enabled functional analyses in D. melanogaster that demonstrate roles for WWOX in reactive oxygen species regulation and metabolism. Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells ty...
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Tumor Suppressor WWOX Contributes to the Elimination of Tumorigenic Cells in Drosophila melanogaster
2015Co-Authors: Louise V. O’keefe, Amanda Choo, Cheng Shoou Lee, Robert I. RichardsAbstract:WWOX is a >1Mb gene spanning FRA16D Common Chromosomal Fragile Site, a region of DNA instability in cancer. Consequently, altered WWOX levels have been observed in a wide variety of cancers. In vitro studies have identified a large number and variety of potential roles for WWOX. Although its normal role in vivo and functional contribution to cancer have not been fully defined, WWOX does have an integral role in metabolism and can suppress tumor growth. Using Drosophila melanogaster as an in vivo model system, we find that WWOX is a modulator of TNFα/Egr-mediated cell death. We found that altered levels of WWOX can modify phenotypes generated by low level ectopic expression of TNFα/Egr and this corresponds to altered levels of Caspase 3 activity. These results demonstrate an in vivo role for WWOX in promoting cell death. This form of cell death is accompanied by an increase in levels of reactive oxygen species, the regulation of which we have previously shown can also be modified by altered WWOX activity. We now hypothesise that, through regulation of reactive oxygen species, WWOX constitutes a link between alterations in cellular metabolism observed in cancer cells and their ability to evade normal cell death pathways. We have further shown that WWOX activity is required for the efficient removal of tumorigenic cells from a developing epithelial tissue. Together these results provide a molecular basis for the tumor suppressor functions of WWOX and the better prognosis observed in cancer patients with higher levels of WWOX activity. Understanding the conserved cellular pathways to which WWOX contributes provides novel possibilities for the development of therapeutic approaches to restore WWOX function in cancer.
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Common Chromosomal Fragile Site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells.
Genes chromosomes & cancer, 2013Co-Authors: Sonia Dayan, Louise V. O'keefe, Amanda Choo, Robert I. RichardsAbstract:The WWOX gene spans the FRA16D common Chromosomal Fragile Site and is able to suppress tumor growth. FRA16D is a frequent Site of DNA instability in cancer resulting in reduced levels of WWOX expression. Altered levels of WWOX have been shown to affect metabolism. Whereas metabolic reprograming of cells from oxidative phosphorylation to aerobic glycolysis is a major hallmark of tumors, the relationship between common Chromosomal Fragile Site genes and altered metabolism has been unclear. Here we report that altering metabolism from glycolysis to oxidative phosphorylation causes stable increase in steady-state levels of transcripts of the WWOX gene. Consistent with this, exposure to hypoxic conditions, in which cells rely on glycolysis, causes a downregulation of WWOX mRNA. The function of WWOX is therefore intimately integrated with metabolism, as WWOX not only contributes to the metabolic state of cells, its transcript levels are also linked to intracellular metabolic state.
Sonia Dayan - One of the best experts on this subject based on the ideXlab platform.
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XML Template (2015) [12.1.2015–12:46pm] [1–7] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/EBMJ/Vol00000/140218/APPFile/SG-EBMJ140218.3d (EBM) [PREPRINTER stage]
2016Co-Authors: Robert I. Richards, Cheng Shoou Lee, A Choo, Sonia DayanAbstract:WWOX, the Chromosomal Fragile Site FRA16D spanning gene: It
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WWOX, the Chromosomal Fragile Site FRA16D spanning gene: Its role in metabolism and contribution to cancer:
Experimental biology and medicine (Maywood N.J.), 2015Co-Authors: Robert I. Richards, Sonia Dayan, Amanda Choo, Cheng Shoou Lee, Louise V. O'keefeAbstract:The WWOX gene spans the common Chromosomal Fragile Site FRA16D that is located within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which may contribute to the very low abundance of the full-length 1.4 kb mRNA. Alternative splicing also accounts for a variety of aberrant transcripts, most of which are devoid of C-terminal sequences required for WWOX to act as an oxidoreductase. The mouse WWOX gene also spans a Chromosomal Fragile Site implying some sort of functional relationship that confers a selective advantage. The encoded protein domains of WWOX are conserved through evolution (between humans and Drosophila melanogaster) and include WW domains, an NAD -binding Site, short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization signals. This homology has enabled functional analyses in D. melanogaster that demonstrate roles for WWOX in reactive oxygen species regulation and metabolism. Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells ty...
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Common Chromosomal Fragile Site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells.
Genes chromosomes & cancer, 2013Co-Authors: Sonia Dayan, Louise V. O'keefe, Amanda Choo, Robert I. RichardsAbstract:The WWOX gene spans the FRA16D common Chromosomal Fragile Site and is able to suppress tumor growth. FRA16D is a frequent Site of DNA instability in cancer resulting in reduced levels of WWOX expression. Altered levels of WWOX have been shown to affect metabolism. Whereas metabolic reprograming of cells from oxidative phosphorylation to aerobic glycolysis is a major hallmark of tumors, the relationship between common Chromosomal Fragile Site genes and altered metabolism has been unclear. Here we report that altering metabolism from glycolysis to oxidative phosphorylation causes stable increase in steady-state levels of transcripts of the WWOX gene. Consistent with this, exposure to hypoxic conditions, in which cells rely on glycolysis, causes a downregulation of WWOX mRNA. The function of WWOX is therefore intimately integrated with metabolism, as WWOX not only contributes to the metabolic state of cells, its transcript levels are also linked to intracellular metabolic state.
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Drosophila orthologue of WWOX, the Chromosomal Fragile Site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species
Human molecular genetics, 2010Co-Authors: Louise V. O'keefe, Sonia Dayan, Amanda Choo, Alexander Colella, Qingwen Chen, Reuben Jacob, Gareth Price, Dean Venter, Robert I. RichardsAbstract:Common Chromosomal Fragile Sites FRA3B and FRA16D are frequent Sites of DNA instability in cancer, but their contribution to cancer cell biology is not yet understood. Genes that span these Sites (FHIT and WWOX, respectively) are often perturbed (either increased or decreased) in cancer cells and both are able to suppress tumour growth. While WWOX has some tumour suppressor characteristics, its normal role and functional contribution to cancer has not been fully determined. We find that a significant proportion of Drosophila Wwox interactors identified by proteomics and microarray analyses have roles in aerobic metabolism. Functional relationships between Wwox and either CG6439/isocitrate dehydrogenase (Idh) or Cu-Zn superoxide dismutase (Sod) were confirmed by genetic interactions. In addition, altered levels of Wwox resulted in altered levels of endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways involving aerobic metabolism and oxidative stress, providing an explanation for the 'non-classical tumour suppressor' behaviour of WWOX. Fragile Sites, and the genes that span them, are therefore part of a protective response mechanism to oxidative stress and likely contributors to the differences seen in aerobic glycolysis (Warburg effect) in cancer cells.
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fra16d common Chromosomal Fragile Site oxido reductase for wwox protects against the effects of ionizing radiation in drosophila
Oncogene, 2005Co-Authors: Louise V Okeefe, Sonia Dayan, Yinghong Liu, Alison Perkins, Robert Saint, Robert I. RichardsAbstract:Fragile Sites are Chromosomal structures that have been proposed to have a determining role in cancer-associated DNA instability. The human WWOX gene spans the FRA16D Chromosomal Fragile Site, the common minimal region of homozygous deletion found in adenocarcinomas and three out of five translocation breakpoints in multiple myeloma. Transcripts from the alternatively spliced WWOX gene encode proteins with common N-terminal WW domains and variable homology to the oxidoreductase family of proteins. In this study, the Drosophila orthologue of the WWOX gene was identified and subjected to mutagenesis via homologous recombination. The resultant DmWWOX1 mutants were viable but exhibited an increased sensitivity to ionizing radiation. This radiation sensitivity was rescued by reintroduction and expression of either the wild-type Drosophila or human WWOX genes. Thus, the protective function of DmWWOX in response to irradiation in Drosophila is conserved with human WWOX (hWWOX). This is consistent with a protective role for hWWOX where aberrant expression, as a result of breakage at the associated Fragile Site, could contribute directly to cancer progression.
C. Marcelo Aldaz - One of the best experts on this subject based on the ideXlab platform.
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WWOX protein expression in normal human tissues
Journal of Molecular Histology, 2006Co-Authors: Maria I. Nunez, John Ludes-meyers, C. Marcelo AldazAbstract:WWOX is a putative tumor suppressor gene that spans approximately a 1 Mb genomic region and is the Site for the second most common Chromosomal Fragile Site, FRA16D at 16q23. Various studies have focused on the expression of WWOX in human cancer mostly at the RNA level, but little is known about the normal pattern of WWOX protein expression in non-neoplastic tissues. In this study, a comprehensive analysis of WWOX protein expression in normal tissues was performed by means of immunohistochemistry utilizing a very specific anti-WWOX polyclonal antibody. We analyzed tissue cores of human samples representing more than 30 organs, using various tissue microarray (TMA) slides. Due to the potential role of WWOX in sex-steroid metabolism, whole sections from hormonally regulated organs like breast, ovaries, testes and prostate were also analyzed. The results from our study indicate that WWOX is preferentially highly expressed in secretory epithelial cells of reproductive, endocrine and exocrine organs, as well as in ductal epithelial cells from specific segments of the urinary system. Interestingly, we also observed significant WWOX protein expression in various cell types of neural origin including neurons, ependymal cells and astrocytes. No expression of WWOX was detected in adipose, connective, and lymphoid tissues, myelinized structures and blood vessels. By better defining the topographic distribution of WWOX in normal tissues this study provides some insight on the potential physiological role of this novel protein.
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Expression of common Chromosomal Fragile Site genes, WWOX/FRA16D and FHIT/FRA3B is downregulated by exposure to environmental carcinogens, UV, and BPDE but not by IR.
Molecular carcinogenesis, 2005Co-Authors: Elangovan Thavathiru, John H. Ludes-meyers, Michael C. Macleod, C. Marcelo AldazAbstract:Common Chromosomal Fragile Sites are unstable genomic loci susceptible to breakage, rearrangement, and are highly recombinogenic. Frequent alterations at these loci in tumor cells led to the hypothesis that they may contribute to cancer development. The two most common Chromosomal Fragile Sites FRA16D and FRA3B which harbor WWOX and FHIT genes, respectively, are frequently altered in human cancers. Here we report that environmental carcinogens, ultraviolet (UV) light, and Benzo[a]pyrene diol epoxide (BPDE), significantly downregulate expression of both genes. On the other hand, we observe that ionizing radiation (IR) does not affect expression of these genes, suggesting that the effect of repression exerted by UV and BPDE is not just a consequence of DNA damage but may be a result of different signaling pathways triggered by specific DNA lesions. Such downregulation correlates with an induction of an S-phase delay in the cell cycle. Treatment of UV-irradiated cells with caffeine abrogates the S-phase delay while concomitantly overcoming the repression phenomenon. This suggests the involvement of unique cell cycle checkpoint mechanisms in the observed repression. Therefore, it is hypothesized that protracted downregulation of the putative tumor suppressor genes WWOX and FHIT by environmental carcinogens may constitute an additional mechanism of relevance in the initiation of tumorigenesis.
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Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status
Breast Cancer Research and Treatment, 2005Co-Authors: Maria I. Nunez, John Ludes-meyers, Martín C. Abba, Nancy W. Abbey, Robert E. Page, Aysegul Sahin, Andrés J. P. Klein-szanto, C. Marcelo AldazAbstract:WWOX is a cancer gene, spanning the common Chromosomal Fragile Site 16D. Genomic and expression aberrations affecting this gene and locus are common in various neoplasias including breast cancer. The aim of the present study was to evaluate the relationship between WWOX expression at the protein level with respect to clinico-pathological characteristics. We performed immunohistochemical analyses on breast specific tissue microarrays representing, human normal breast epithelium ( n =16), ductal carcinoma in situ ( n =15) and invasive breast cancer cases ( n =203). Staining intensity measurements were objectively determined utilizing an image analysis system. Western blot analyses were also performed on an independent set of 23 invasive breast carcinomas. All normal breast epithelial samples express WWOX protein abundantly while 34% (69/203 cases) of invasive breast carcinomas were ‘completely negative’ for WWOX expression and an additional 26% (52/203) of cases expressed WWOX very weakly. For DCIS samples five out of 15 (33%) were negative or weak for WWOX staining. Interestingly, we found a statistically significant correlation between WWOX expression and estrogen receptor (ER) status, 27% of ER+ breast carcinomas were completely negative for WWOX expression versus 46% for ER−cases ( p = 0.0054). Furthermore, when negative plus weakly WWOX stained cases were considered the difference became more significant with 51% of ER+ cases and 73% for the ER − group, with a p = 0.003. These data indicate that loss of WWOX expression is a common event in breast cancer. It is unclear at this point whether loss of WWOX expression is a consequence of tumor progression or represents a subclass of breast carcinomas. The strong association of WWOX expression with ER status reinforces the suggested role of this protein as an enzyme involved in sex steroid metabolism.
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Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status
Breast Cancer Research and Treatment, 2005Co-Authors: Maria I. Nunez, John Ludes-meyers, Hyunsuk Kil, Martín C. Abba, Nancy W. Abbey, Robert E. Page, Aysegul Sahin, Andrés J. P. Klein-szanto, C. Marcelo AldazAbstract:WWOX is a cancer gene, spanning the common Chromosomal Fragile Site 16D. Genomic and expression aberrations affecting this gene and locus are common in various neoplasias including breast cancer. The aim of the present study was to evaluate the relationship between WWOX expression at the protein level with respect to clinico-pathological characteristics. We performed immunohistochemical analyses on breast specific tissue microarrays representing, human normal breast epithelium ( n =16), ductal carcinoma in situ ( n =15) and invasive breast cancer cases ( n =203). Staining intensity measurements were objectively determined utilizing an image analysis system. Western blot analyses were also performed on an independent set of 23 invasive breast carcinomas. All normal breast epithelial samples express WWOX protein abundantly while 34% (69/203 cases) of invasive breast carcinomas were ‘completely negative’ for WWOX expression and an additional 26% (52/203) of cases expressed WWOX very weakly. For DCIS samples five out of 15 (33%) were negative or weak for WWOX staining. Interestingly, we found a statistically significant correlation between WWOX expression and estrogen receptor (ER) status, 27% of ER+ breast carcinomas were completely negative for WWOX expression versus 46% for ER−cases ( p = 0.0054). Furthermore, when negative plus weakly WWOX stained cases were considered the difference became more significant with 51% of ER+ cases and 73% for the ER − group, with a p = 0.003. These data indicate that loss of WWOX expression is a common event in breast cancer. It is unclear at this point whether loss of WWOX expression is a consequence of tumor progression or represents a subclass of breast carcinomas. The strong association of WWOX expression with ER status reinforces the suggested role of this protein as an enzyme involved in sex steroid metabolism.
Louise V. O'keefe - One of the best experts on this subject based on the ideXlab platform.
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WWOX, the Chromosomal Fragile Site FRA16D spanning gene: Its role in metabolism and contribution to cancer:
Experimental biology and medicine (Maywood N.J.), 2015Co-Authors: Robert I. Richards, Sonia Dayan, Amanda Choo, Cheng Shoou Lee, Louise V. O'keefeAbstract:The WWOX gene spans the common Chromosomal Fragile Site FRA16D that is located within a massive (780 kb) intron. The WWOX gene is very long, at 1.1 Mb, which may contribute to the very low abundance of the full-length 1.4 kb mRNA. Alternative splicing also accounts for a variety of aberrant transcripts, most of which are devoid of C-terminal sequences required for WWOX to act as an oxidoreductase. The mouse WWOX gene also spans a Chromosomal Fragile Site implying some sort of functional relationship that confers a selective advantage. The encoded protein domains of WWOX are conserved through evolution (between humans and Drosophila melanogaster) and include WW domains, an NAD -binding Site, short-chain dehydrogenase/reductase enzyme and nuclear compartmentalization signals. This homology has enabled functional analyses in D. melanogaster that demonstrate roles for WWOX in reactive oxygen species regulation and metabolism. Indeed the human WWOX gene is also responsive to altered metabolism. Cancer cells ty...
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Common Chromosomal Fragile Site FRA16D tumor suppressor WWOX gene expression and metabolic reprograming in cells.
Genes chromosomes & cancer, 2013Co-Authors: Sonia Dayan, Louise V. O'keefe, Amanda Choo, Robert I. RichardsAbstract:The WWOX gene spans the FRA16D common Chromosomal Fragile Site and is able to suppress tumor growth. FRA16D is a frequent Site of DNA instability in cancer resulting in reduced levels of WWOX expression. Altered levels of WWOX have been shown to affect metabolism. Whereas metabolic reprograming of cells from oxidative phosphorylation to aerobic glycolysis is a major hallmark of tumors, the relationship between common Chromosomal Fragile Site genes and altered metabolism has been unclear. Here we report that altering metabolism from glycolysis to oxidative phosphorylation causes stable increase in steady-state levels of transcripts of the WWOX gene. Consistent with this, exposure to hypoxic conditions, in which cells rely on glycolysis, causes a downregulation of WWOX mRNA. The function of WWOX is therefore intimately integrated with metabolism, as WWOX not only contributes to the metabolic state of cells, its transcript levels are also linked to intracellular metabolic state.
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Drosophila orthologue of WWOX, the Chromosomal Fragile Site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species
Human molecular genetics, 2010Co-Authors: Louise V. O'keefe, Sonia Dayan, Amanda Choo, Alexander Colella, Qingwen Chen, Reuben Jacob, Gareth Price, Dean Venter, Robert I. RichardsAbstract:Common Chromosomal Fragile Sites FRA3B and FRA16D are frequent Sites of DNA instability in cancer, but their contribution to cancer cell biology is not yet understood. Genes that span these Sites (FHIT and WWOX, respectively) are often perturbed (either increased or decreased) in cancer cells and both are able to suppress tumour growth. While WWOX has some tumour suppressor characteristics, its normal role and functional contribution to cancer has not been fully determined. We find that a significant proportion of Drosophila Wwox interactors identified by proteomics and microarray analyses have roles in aerobic metabolism. Functional relationships between Wwox and either CG6439/isocitrate dehydrogenase (Idh) or Cu-Zn superoxide dismutase (Sod) were confirmed by genetic interactions. In addition, altered levels of Wwox resulted in altered levels of endogenous reactive oxygen species. Wwox (like FHIT) contributes to pathways involving aerobic metabolism and oxidative stress, providing an explanation for the 'non-classical tumour suppressor' behaviour of WWOX. Fragile Sites, and the genes that span them, are therefore part of a protective response mechanism to oxidative stress and likely contributors to the differences seen in aerobic glycolysis (Warburg effect) in cancer cells.
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FRA16D common Chromosomal Fragile Site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila.
Oncogene, 2005Co-Authors: Louise V. O'keefe, Sonia Dayan, Yinghong Liu, Alison Perkins, Robert Saint, Robert I. RichardsAbstract:Fragile Sites are Chromosomal structures that have been proposed to have a determining role in cancer-associated DNA instability. The human WWOX gene spans the FRA16D Chromosomal Fragile Site, the common minimal region of homozygous deletion found in adenocarcinomas and three out of five translocation breakpoints in multiple myeloma. Transcripts from the alternatively spliced WWOX gene encode proteins with common N-terminal WW domains and variable homology to the oxidoreductase family of proteins. In this study, the Drosophila orthologue of the WWOX gene was identified and subjected to mutagenesis via homologous recombination. The resultant DmWWOX1 mutants were viable but exhibited an increased sensitivity to ionizing radiation. This radiation sensitivity was rescued by reintroduction and expression of either the wild-type Drosophila or human WWOX genes. Thus, the protective function of DmWWOX in response to irradiation in Drosophila is conserved with human WWOX (hWWOX). This is consistent with a protective role for hWWOX where aberrant expression, as a result of breakage at the associated Fragile Site, could contribute directly to cancer progression.
Yuh-hwa Wang - One of the best experts on this subject based on the ideXlab platform.
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doi:10.1155/2012/927683 Review Article The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma
2016Co-Authors: Laura W. Dillon, Christine E. Lehman, Yuh-hwa WangAbstract:License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of Chromosomal Fragile Site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal Fragile Sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce Fragile Site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of Fragile Site breakage in PTC development, external Fragile Site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women. 1
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The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma
Journal of thyroid research, 2012Co-Authors: Laura W. Dillon, Christine E. Lehman, Yuh-hwa WangAbstract:The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of Chromosomal Fragile Site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal Fragile Sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce Fragile Site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of Fragile Site breakage in PTC development, external Fragile Site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women.