Frizzled-7 promoter is highly active in tumors and promoter-driven Shiga-like toxin I inhibits hepatocellular carcinoma growth.
Frizzled-7 protein plays a significant role in the formation of several malignant tumors. Up regulation of the Frizzled-7 in cancer cell lines is associated with nuclear accumulation of wild-type β-catenin from the Wnt/β-catenin pathway which is frequently activated in tumors. To analyze activity of the Frizzled-7 promoter in tumor cells, we constructed two recombinant plasmid vectors in which the Frizzled-7 promoter was used to drive the expression of green fluorescent protein (GFP) and Shiga-like toxin I (Stx1) (pFZD7-GFP/Stx1) genes. The Frizzled-7 protein was found to be expressed in the cancer cell lines but not in the normal cell lines. The GFP expression was restricted to the cancer cell lines and xenografts in the BALB/C mice but not to normal cell lines. Moreover, cell proliferation and tumor growth decreased significantly after transfection with the pFZD7-Stx1. Results from this study will help determine a highly effective strategy for gene therapy of tumors.
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Hongpan
H
Xu
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Lailing
L
Gong
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Yanyan
Y
Xia
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Lili
L
Qu
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Qiwen
Q
Li
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Lu
L
Pang
Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
Jin
J
Si
Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.
Zhiyang
Z
Li
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022622:Shiga Toxin 1 / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
C115810:FZD7 protein, human; D051157:Frizzled Receptors; D022622:Shiga Toxin 1
Frizzled-7 promoter; Shiga-like toxin I; gene therapy; pFZD7-GFP; pFZD7-Stx1