Katoh Masaru
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Int J Oncol. 2003 Jan;22(1):209-12.
WNT family of secreted-type glycoproteins play key roles in carcinogenesis and embryogenesis. We have cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14 and WNT14B/WNT15 using bioinformatics and cDNA-PCR, and also reported frequent up-regulation of WNT2 in primary gastric cancer. Here, expression and regulation of WNT1 in human cancer were investigated using cDNA-PCR. WNT1 mRNA was relatively highly expressed in OKAJIMA cells (gastric cancer) and BxPC-3 cells (pancreatic cancer). Expression of WNT1 mRNA was up-regulated in 5 out of 10 cases of primary gastric cancer. Effects of beta-estradiol on expression of human WNT1 in MCF-7 cells (breast cancer) was next investigated, because mouse Wnt-1 induces mammary carcinogenesis even in estrogen receptor alpha (ERalpha) knockout mice. Expression of WNT1 mRNA was significantly up-regulated by beta-estradiol in MCF-7 cells. WNT1 was found to be one of estrogen target genes in human MCF-7 cells, which in part explains Wnt1-induced mammary carcinogenesis in ERalpha knockout mice.
分泌型糖蛋白的WNT家族在致癌作用和胚胎发育过程中发挥关键作用。我们利用生物信息学和cDNA-PCR技术克隆并鉴定了人WNT2B/WNT13、WNT3、WNT3A、WNT5B、WNT6、WNT7B、WNT8A、WNT8B、WNT10A、WNT10B、WNT11、WNT14以及WNT14B/WNT15，并且还报道了原发性胃癌中WNT2的频繁上调。在此，我们利用cDNA-PCR技术研究了WNT1在人类癌症中的表达及调控情况。WNT1 mRNA在冈岛细胞（胃癌）和BxPC-3细胞（胰腺癌）中相对高表达。在10例原发性胃癌病例中，有5例WNT1 mRNA的表达上调。接下来研究了β-雌二醇对人MCF-7细胞（乳腺癌）中WNT1表达的影响，因为小鼠Wnt-1即使在雌激素受体α（ERα）基因敲除小鼠中也能诱导乳腺癌发生。在MCF-7细胞中，β-雌二醇可显著上调WNT1 mRNA的表达。发现WNT1是人类MCF-7细胞中的雌激素靶基因之一，这在一定程度上解释了Wnt1在ERα基因敲除小鼠中诱导乳腺癌发生的原因。
