Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells.
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.
Katoh
Masaru
M
Genetics and Cell Biology Section, Genetics Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan. mkatoh@ncc.go.jp
D000199:Actins / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins
D000199:Actins; D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins; D004958:Estradiol