FRA16D common chromosomal fragile site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila

O’Keefe, Louise V.; Liu, Yanping; Perkins, Alison J.; Dayan, Sonia; Saint, Robert; Richards, Robert I.

doi:10.1038/sj.onc.1208806

Cited by 23 publications

(27 citation statements)

References 31 publications

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“…A number of the other large CFS genes have also been suggested to function as tumor suppressors (Liu et al, 2000;Cesari et al, 2003;Denison et al, 2003a;Zhu et al, 2006) but this has not yet been demonstrated. Several of the large CFS genes including FHIT, WWOX, and RORA have been shown to be involved in cellular responses to stress (Ottey et al, 2004;Chen et al, 2005;O'Keefe et al, 2005;Thavathiru et al, 2005;Nakagawa and Akao, 2006;Zhu et al, 2006). Finally, a number of these genes, including PARK2, GRID2, and RORA have been shown to be involved in normal neurological development (Dussault et al, 1998;Kitada et al, 1998;Lorenzetti et al, 2004;Rozier et al, 2004).…”

Section: Discussionmentioning

confidence: 96%

Disabled‐1 is a large common fragile site gene, inactivated in multiple cancers

McAvoy

Zhu

Perez

et al. 2007

Genes Chromosomes & Cancer

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Common fragile sites (CFS) are large, genomically unstable regions, which are hot-spots for deletions and other alterations, especially in cancer cells. Several have been shown to contain genes that span large genomic regions, such as FHIT (1.5 Mb), WWOX (1.0 Mb), GRID2 (1.36 Mb), PARK2 (1.3 Mb), and RORA (730 kb). These genes are frequently inactivated in multiple different cancers, and FHIT and WWOX are shown to function as tumor suppressors. The disabled-1 gene (DAB1) is one of the human homologs of the Drosophila disabled locus, which in mammals is involved in neuronal migration and lamination in the developing cerebral cortex. Mice DAB1 inactivation results in the neurological mutant Scrambler, having similarities to mice with the inactivation of PARK2 (Quaker), GRID2 (Lurcher), and RORA (Staggerer). We were interested in whether DAB1 was another large CFS gene that could have cancer development importance. We demonstrated here that the human DAB1 gene (spanning 1.25 Mb) mapped within FRA1B CFS region on chromosomal band 1p32.2. Real-time RT-PCR analysis revealed that the expression level of DAB1 was decreased in many human cancer samples, including primary tumor tissues and cancer-derived cell lines, from several different cancers, especially in brain and endometrial cancer. Additionally, the introduction of an over-expression DAB1 plasmid into two different cell lines, having insignificant endogenous DAB1 expression, resulted in decreased cell growth. In summary, DAB1 is another gene that resides within an unstable CFS region and might play a role in human tumorigenesis. These data may provide further linkage between neurological development and cancer.

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Section: Discussionmentioning

confidence: 96%

Disabled‐1 is a large common fragile site gene, inactivated in multiple cancers

McAvoy

Zhu

Perez

et al. 2007

Genes Chromosomes & Cancer

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“…Downregulation of WOX1 and WOX2 promotes neurodegeneration in Alzheimer's disease, suggesting its protective role against neurodegeneration [43]. FOR (WWOX/WOX1) is shown to protect against the effects of ionizing radiation in Drosophila [44]. These observations support a pro-survival role of WOX1 in vivo [4].…”

Section: Discussionmentioning

confidence: 99%

Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-κB, JNK1, p53 and WOX1 during stress response

et al. 2007

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Background: Zfra is a 31-amino-acid zinc finger-like protein, which is known to regulate cell death by tumor necrosis factor (TNF) and overexpressed TNF receptor-or Fas-associated death domain proteins (TRADD and FADD). In addition, Zfra undergoes self-association and interacts with c-Jun N-terminal kinase 1 (JNK1) in response to stress stimuli. To further delineate the functional properties of Zfra, here we investigated Zfra regulation of the activation of p53, WOX1 (WWOX or FOR), NF-κB, and JNK1 under apoptotic stress.

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“…WWOX is highly expressed in secretory epithelial cells, endocrine and exocrine organs, and urinary epithelial cells [18]. WWOX has tumor suppressor properties [19] and has been implicated in breast [14,[20][21][22][23][24][25][26], ovarian [27][28][29], prostate [30][31][32], oral [33,34], gastric [35,36], pancreatic [37], esophageal [38], cutaneous [39][40][41][42], thyroid [43] and lung carcinomas [25,[44][45][46][47][48] and meningiomas [49].…”

Section: Introductionmentioning

confidence: 99%