Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Oncol Rep. 2005 Sep;14(3):783-7.
SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, DKK1, DKK2, DKK3, DKK4, and WIF1 are soluble modulators of WNT signaling. SFRP2 gene at human chromosome 4q31.3 is claimed as a tumor suppressor gene inactivated by the epigenetic CpG hypermethylation in colorectal cancer. SFRP2 methylation is a sensitive single DNA-based marker for the fecal screening of colorectal cancer. On the other hand, SFRP2 is claimed to induce cellular resistance to apoptosis in mammary tumors. Here, we identified and characterized the rat Sfrp2 gene by using bioinformatics. Rat Sfrp2 gene, consisting of three exons, was located within AC129161.3 genome sequence. Rat Sfrp2 gene was found to encode a 295-aa Sfrp2 protein, consisting of signal peptide, Frizzled domain with ten conserved Cys residues, and Netrin (NTR) domain with six conserved Cys residues. Rat Sfrp2 showed 98.6% and 97.6% total-amino-acid identity with mouse Sfrp2 and human SFRP2, respectively. Phylogenetic analyses revealed that Sfrp2 orthologs were more related to Sfrp1 and Sfrp5 orthologs than to Sfrp3 and Sfrp4 orthologs. Human SFRP2 promoter (nucleotide position 71417-71152 of AC020703.7 genome sequence) and rat Sfrp2 promoter (nucleotide position 184090-184357 of AC129161.3 genome sequence) showed 88.7% total nucleotide identity. GC content of human SFRP2 promoter was 63.9%. Binding site for POU domain transcription factors (POU2F1, POU2F2, etc.) was conserved between human SFRP2 promoter and rat Sfrp2 promoter. SFRP2 mRNA was expressed in embryonic stem (ES) cells, diffuse type gastric cancer with signet ring cell features, pancreatic cancer, colorectal cancer, retinoblastoma, and insulinoma. This is the first report on comparative integromics analyses on SFRP2 orthologs.
SFRP1、SFRP2、SFRP3、SFRP4、SFRP5、DKK1、DKK2、DKK3、DKK4和WIF1是WNT信号通路的可溶性调节因子。位于人类染色体4q31.3的SFRP2基因被认为是一种肿瘤抑制基因，在结直肠癌中因表观遗传的CpG高甲基化而失活。SFRP2甲基化是用于结直肠癌粪便筛查的一种基于单个DNA的敏感标志物。另一方面，SFRP2被认为可诱导乳腺肿瘤细胞产生抗凋亡能力。在此，我们利用生物信息学鉴定并表征了大鼠Sfrp2基因。大鼠Sfrp2基因由三个外显子组成，位于AC129161.3基因组序列内。发现大鼠Sfrp2基因编码一种295个氨基酸的Sfrp2蛋白，该蛋白由信号肽、具有10个保守半胱氨酸残基的卷曲蛋白结构域以及具有6个保守半胱氨酸残基的网蛋白（NTR）结构域组成。大鼠Sfrp2与小鼠Sfrp2和人类SFRP2的总氨基酸同一性分别为98.6%和97.6%。系统发育分析表明，Sfrp2直系同源物与Sfrp1和Sfrp5直系同源物比与Sfrp3和Sfrp4直系同源物的关系更密切。人类SFRP2启动子（AC020703.7基因组序列的核苷酸位置71417 - 71152）和大鼠Sfrp2启动子（AC129161.3基因组序列的核苷酸位置184090 - 184357）的总核苷酸同一性为88.7%。人类SFRP2启动子的GC含量为63.9%。POU结构域转录因子（POU2F1、POU2F2等）的结合位点在人类SFRP2启动子和大鼠Sfrp2启动子之间保守。SFRP2 mRNA在胚胎干细胞、具有印戒细胞特征的弥漫型胃癌、胰腺癌、结直肠癌、视网膜母细胞瘤和胰岛素瘤中表达。这是关于SFRP2直系同源物的比较整合组学分析的首次报道。
