Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Int J Mol Med. 2002 Jun;9(6):579-84.
WNT signals are transduced to beta-catenin - TCF pathway, JNK pathway, or Ca2+-releasing pathway through WNT receptors. FRAT1, FRAT2, and PAR-1 are positive regulators of WNT - beta-catenin pathway. APC, AXIN, NKD1, NKD2, and Strabismus (STB1, STB2) are negative regulators of WNT - beta-catenin pathway. Here, biological significance of WNT3-WNT14B/WNT15 gene cluster (human chromosome 17q21) and WNT3A-WNT14 gene cluster (human chromosome 1q42) will be reviewed. Total-amino-acid identity between WNT3 and WNT3A is 84.2%, and that between WNT14 and WNT14B is 61.4%. WNT3A and WNT14B show reciprocal regulation by all-trans retinoic acid in NT2 cells and by beta-estradiol in MCF-7 cells. Exon-intron structures are well conserved between WNT3-WNT14B gene cluster and WNT3A-WNT14 gene cluster, except for the existence of an additional intron in 3'-UTR of WNT3. Capicua pseudogene and AK024248-related sequence are located within intergenic region of human WNT3A-WNT14 gene cluster, but not within intergenic regions of human WNT3-WNT14B gene cluster and mouse Wnt3a-Wnt14 gene cluster. Integration of mouse mammary tumor virus (MMTV) into mouse Wnt3-Wnt14b gene cluster leads to carcinogenesis. Because these WNT gene clusters might be fragile sites in the human genome, implication of WNT3 or WNT3A in cancer as well as implication of WNT14 or WNT14B in connective tissue disease and congenital joint malformation should be elucidated in the future. WNT3, WNT3A, WNT14, and WNT14B might be applicable to tissue engineering of neuron and joint in the field of regenerative medicine, and as an early diagnostic marker in the field of clinical oncology.
WNT信号通过WNT受体转导至β-连环蛋白-TCF途径、JNK途径或Ca2+释放途径。FRAT1、FRAT2和PAR-1是WNT-β-连环蛋白途径的正调节因子。APC、AXIN、NKD1、NKD2和斜视（STB1、STB2）是WNT-β-连环蛋白途径的负调节因子。在此，将综述WNT3-WNT14B/WNT15基因簇（人类染色体17q21）和WNT3A-WNT14基因簇（人类染色体1q42）的生物学意义。WNT3和WNT3A之间的总氨基酸同一性为84.2%，WNT14和WNT14B之间的总氨基酸同一性为61.4%。WNT3A和WNT14B在NT2细胞中受全反式维甲酸以及在MCF-7细胞中受β-雌二醇的相互调节。WNT3-WNT14B基因簇和WNT3A-WNT14基因簇之间的外显子-内含子结构高度保守，除了WNT3的3'-UTR中存在一个额外的内含子。Capicua假基因和AK024248相关序列位于人类WNT3A-WNT14基因簇的基因间隔区内，但不在人类WNT3-WNT14B基因簇和小鼠Wnt3a-Wnt14基因簇的基因间隔区内。小鼠乳腺肿瘤病毒（MMTV）整合到小鼠Wnt3-Wnt14b基因簇中会导致癌变。由于这些WNT基因簇可能是人类基因组中的脆弱位点，未来应阐明WNT3或WNT3A在癌症中的作用以及WNT14或WNT14B在结缔组织疾病和先天性关节畸形中的作用。WNT3、WNT3A、WNT14和WNT14B可能适用于再生医学领域的神经元和关节组织工程，以及临床肿瘤学领域的早期诊断标志物。
