Sox18 mutations in the ragged mouse alleles ragged‐like and opossum

James, Kristy; Hosking, Brett; Gardner, J. L.; Muscat, George E.O.; Koopman, Peter

doi:10.1002/gene.10190

Cited by 64 publications

(68 citation statements)

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“…[19][20][21][22][23][24][25][26][27][28][29][30] In fact, few studies have revealed the significance of SOX group F gene expression in human cancer, although cell line-based studies have demonstrated that both SOX 18 and SOX 7 were highly expressed in several strains of gastric, pancreatic and esophageal cancer cell lines. 22,32 In the present study, SOX group F gene expression determined by RT-PCT was increased in gastric cancer tissues than in normal gastric tissues obtained from the same individuals.…”

Section: Discussionmentioning

confidence: 99%

“…23,24 Thus, interfering with SOX 18 function, both blood vessel formation and subsequent tumor growth are inhibited and this process is responsible for the lymphatic defect in hypotrichosis-lymphoedema-telangiectasia. [25][26][27][28] The SOX 7 and SOX 17 genes are also known to have compensatory roles during angiogenesis and lymphangiogenesis. [19][20][21] It has been demonstrated that blood circulation in SOX 7 and SOX 18 double knock-down zebrafish was blocked in the trunk and tail due to multiple fusions between the axial vessels.…”

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confidence: 99%

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The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

Eom¹,

Jo²,

Kook³

et al. 2011

Intl Journal of Cancer

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SOX group F genes are important regulators of angiogenesis and lymphangiogenesis. The aim of the present study was to examine the relationships between Sox group F expression and clinicopathological factors in gastric cancer. Three hundred and fifteen gastric cancer tissues and the corresponding normal gastric tissue were obtained from the tumor bank at the National Cancer Center, Korea. SOX group F mRNA levels in these tissues were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The serum levels of SOX 18 proteins in 219 gastric cancer patients and in 30 healthy volunteers were also measured by enzyme-linked immunosorbent assay. Furthermore, immunohistochemistry (IHC) was performed on 679 gastric cancer tissues and the clinicopathological characteristics, as well as the survival rates of SOX 18 positive and negative gastric cancers were compared. RT-PCR showed that SOX group F mRNA was increased in the gastric cancer tissues compared to the normal gastric tissues (p < 0.001, respectively). The serum levels of SOX 18 protein were also increased in gastric cancer patients compared to healthy volunteers. IHC showed that of the 679 gastric cancer cases, 177 (26.1%) were positive for SOX 18 expression in their tumor stroma, and the frequencies of both lymphovascular invasion and lymph node metastases were higher in the SOX 18 positive than in the negative group. Both the 5-year survival and the recurrence-free survival were shorter for SOX 18 positive tumors (p 5 0.023 and 0.012, respectively). SOX 18 expression might be a prognostic tumor marker and a potential therapeutic target in gastric cancer.Gastric cancer is the fourth most common cancer in the world and, annually, about 1 million new cases are diagnosed worldwide. 1 In South Korea, gastric cancer has a higher incidence than any other cancer, and is the third most common cause of death from cancer. 2 The prognosis of patients with gastric cancer is influenced by the presence of lymph node (LN) metastasis, therefore, an accurate and reliable indicator is required to predict the presence of LN metastasis. Furthermore, a biomolecular predictor of LN metastasis can be a prognostic marker or a potential therapeutic target. [3][4][5] Recently, angiogenesis and lymphangiogenesis were found to be critically required for solid tumor growth, invasion and distant metastases. 6-8 Previous molecular and cellular analyses have identified a number of factors of angiogenesis and lymphangiogenesis, such as, the fibroblast growth factor, the vascular endothelial growth factor and angiopoietin. 9-13 Similarly, specific gene-based studies recently discovered the lymphangiogenesis associated SOX genes (i.e., sex determining region Y box genes). 14,15 The SOX genes constitute a large family of diverse and well-conserved genes, which encode transcription factors. [16][17][18] Members of this gene family are subdivided on a homology basis into ten groups (A to J), and SOX group F comprises the SOX 7, 17 and 18 genes. 17 SOX 18 is transiently expressed in the ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

Eom¹,

Jo²,

Kook³

et al. 2011

Intl Journal of Cancer

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“…The naturally occurring Sox18 mutations in mice and humans (15,20) display defects in hair and skin development. However, the most life threatening is the generalized edema caused by lymphatic vascular dysfunction (17)(18)(19).…”

Section: Cell-specific Transcription Of the Mouse Vcam-1 Is Regulatedmentioning

confidence: 99%

“…In situ analysis of Sox18 has demonstrated expression in the mesenchyme underlying the developing hair follicle, in the presumptive heart, and in the developing vasculature (10). The naturally occurring mouse mutant ragged (Ra) of which there are four allelic variants, Ra, ragged Jackson (RaJ), ragged-like (Ragl) and RaOP, all contain mutations in Sox18 (15). All these mutants display defects in hair and skin development.…”

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confidence: 99%

The VCAM-1 Gene That Encodes the Vascular Cell Adhesion Molecule Is a Target of the Sry-related High Mobility Group Box Gene, Sox18

Hosking

Wang

Downes

et al. 2004

Journal of Biological Chemistry

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VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosislymphedema-telangiectasia disorder.

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“…1C, Ra Op/+ ). The Ra Op mutant mice carry a natural mutation in the Sox18 [SRY (sex determining region Y) box 18] gene (11,12) that triggers the production of a truncated nonfunctional protein that suppresses F-group SOX (Sox7, Sox17, and Sox18) proteins in blood vessels. During lymphangiogenesis, Sox18 is expressed in venous cells to induce Prox-1 expression (11); at the same embryonic stages, Foxc1 and Foxc2 are required to maintain artery vs. vein specification (13).…”

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confidence: 99%

Studies on Axenfeld–Rieger syndrome patients and mice reveal Foxc1's role in corneal neovascularization

François¹,

Ramchandran²

2012

Proc. Natl. Acad. Sci. U.S.A.

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Sox18 mutations in the ragged mouse alleles ragged‐like and opossum

Cited by 64 publications

References 41 publications

The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

The VCAM-1 Gene That Encodes the Vascular Cell Adhesion Molecule Is a Target of the Sry-related High Mobility Group Box Gene, Sox18

Studies on Axenfeld–Rieger syndrome patients and mice reveal Foxc1's role in corneal neovascularization

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