Transfection of nm23-H1 increased expression of beta-Catenin, E-Cadherin and TIMP-1 and decreased the expression of MMP-2, CD44v6 and VEGF and inhibited the metastatic potential of human non-small cell lung cancer cell line L9981.
Nm23 is a metastasis suppressor gene. In this report, we transfected nm23-H1 cDNA into L9981, a human large cell lung cancer cell line with nm23 negative expression, and made a stable transfectant. L9981-nm23-H1 cells exhibited lower cells proliferation rate, more G0/G1 phase growth and an increase in apoptosis with a dramatic decreased in the tumor cells ability to metastasize. L9981-nm23-H1 cells also demonstrated a significantly reduced lymph node and pulmonary metastatic capacity in vivo when injected into the nude mice. Furthermore, we used DNA microarray analysis to explore the change in expression of the metastasis-related genes in L9981-nm23-H1 cells. We found that the expression of beta-Catenin, E-Cadherin and TIMP-1 were significantly increased while expression MMP-2, CD44v6, and VEGF was dramatically decreased in L9981-nm23-H1, as confirmed by RT-PCR and western blot. These results demonstrated that nm23-H1 can suppress the mobility and metastatic capacity of cancer cells and the molecular mechanism by which nm23-H1 suppresses tumor metastasis may be via increasing the expression of metastasis-related genes such as beta-Catenin, E-Cadherin and TIMP-1 and decreasing the expression of MMP-2, CD44V6 and VEGF.
Che
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The Key Laboratory of Lung Cancer Molecular Biology in Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.
Chen
J
J
Liu
L
L
Wang
Y
Y
Li
L
L
Qin
Y
Y
Zhou
Q
Q
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D000818:Animals; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D015820:Cadherins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D054778:NM23 Nucleoside Diphosphate Kinases; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020778:Matrix Metalloproteinase 2