Disease relevance of SOX18

• Expression level of SOX18 mRNA in MCF-7 cells (breast cancer) was not affected by beta-estradiol [1].
• SOX18 mRNA was relatively highly expressed in TMK1 and MKN45 among 7 gastric cancer cell lines [1].
• SOX18 mRNA was expressed in all out of 7 pancreatic cancer cell lines, and was relatively highly expressed in PANC-1, Hs700T, Hs766T and MIA PaCa-2 [1].

High impact information on SOX18

• Two of the families were consanguineous; in affected members of these families, we identified homozygous missense mutations in the SOX18 gene, located in 20q13 [2].
• Thus, we show that SOX18 mutations in humans cause both recessive and dominant hypotrichosis-lymphedema-telangiectasia, suggesting that, in addition to its established role in hair and blood vessel development, the SOX18 transcription factor plays a role in the development and/or maintenance of lymphatic vessels [2].
• Random mutagenesis coupled with GAL4 hybrid analysis in the activation domain between amino acids 252 and 346, of Sox18, implicated the phosphorylation motif, SARS, and the region between amino acid residues 313 and 346 as critical components of Sox18 mediated transactivation [3].
• We initially published the identification and partial cDNA sequence of murine Sox18, a new member of this gene family, isolated from a cardiac cDNA library [3].
• Recently, we demonstrated that mutations in the Sox18 activation domain underlie cardiovascular and hair follicle defects in the mouse mutation, ragged (Ra) (Pennisi et al., 2000. Mutations in Sox18 underlie cardiovascular and hair follicle defecs in ragged mice. Nat. Genet. 24, 434-437) [3].

Biological context of SOX18

• SOX18 is a transcription factor that is transiently expressed in nascent endothelial cells during embryonic development and adult neovascularization [4].
• cDNA cloning, tissue expression, and chromosome mapping of human homolog of SOX18 [5].
• CONCLUSIONS: Our results indicate that SOX18 is involved in vascular cell growth and suggest that this transcription factor may play a role in atherosclerosis [6].
• Mapping analysis has revealed that SOX18 gene is located on human chromosome 20q13.3, 27.29 cR distal from the marker D20S173 [7].
• We also assessed the affects of disrupted SOX18 function on MCF-7 human breast cancer and human umbilical vein endothelial cell (HUVEC) proliferation by measuring BrdU incorporation and by MTS assay, cell migration using Boyden chamber assay, and capillary tube formation in vitro [8].

Anatomical context of SOX18

• SOX18 directly interacts with MEF2C in endothelial cells [9].
• SOX18 and the transcriptional regulation of blood vessel development [4].
• SOX18 mRNA was relatively highly expressed in stomach and jejunum in the gastrointestinal tract [1].
• Northern blot analysis revealed that a 1.9-kb band of human SOX18 messenger RNAs was predominantly expressed in heart, although weak signals were seen in brain, liver, testis, and leukocyte [5].
• Significant SOX18 mRNA levels (by Northern blot analysis and reverse transcription-polymerase chain reaction) were detected in cell cultures from human umbilical vein endothelial cells and human VSMCs [6].

Associations of SOX18 with chemical compounds

• METHODS AND RESULTS: In advanced human coronary atherosclerotic lesions, SOX18 immunostaining was localized in endothelial cells (on the luminal surface, in vasa vasorum, and in intimal neovessels) and in vascular smooth muscle cells (VSMCs) scattered in the intima, colocalizing with proliferating cell nuclear antigen [6].

Regulatory relationships of SOX18

• Interestingly, MEF2C fails to interact or co-activate transcription with the Ra or RaJ mutant SOX18 proteins [9].

Other interactions of SOX18

• These results suggest that MEF2C and SOX18 may be important partners directing the transcriptional regulation of vascular development [9].
• We have previously cloned and characterized human SOX17, constituting a subfamily with SOX7 and SOX18 [10].
• OBJECTIVE: SOX18, a member of the SOX gene family (SRY-like 3-hydroxy-3-methylglutaryl box gene), is a transcription factor expressed in the development of blood vessels during embryogenesis [6].

Analytical, diagnostic and therapeutic context of SOX18

• Here, expression of SOX18 mRNA was investigated using Northern blot analysis, RNA dot blot analysis, and cDNA-PCR [1].
• In cell cultures, SOX18 was mainly localized in subconfluent and denuded areas [6].
• Finally, we examined the expression of Sox18 in multiple adult mouse tissues using RT-PCR [3].

References