TY - JOUR
T1 - Alteration in gene expression profile and biological behavior in human lung cancer cell line NL9980 by nm23-H1 gene silencing
AU - Ma, Wei
AU - Chen, Jun
AU - Xue, Xingyang
AU - Wang, Zhuomin
AU - Liu, Hongyu
AU - Wang, Ting
AU - Bai, Yun
AU - Tang, Shou-Ching
AU - Zhou, Qinghua
N1 - Funding Information:
This work was supported by grants from Key Project of National Natural Science Foundation of China (30430300) and Major Project of Tianjin Sci-Tech Support Program (07SYSYSF05000) and Key Project of Tianjin Sci-Tech Support Program (06YFSZSF05300) to Qinghua Zhou.
PY - 2008/7/4
Y1 - 2008/7/4
N2 - Lung cancer is the leading cause of cancer death in both men and women. Tumor metastasis is an essential aspect of lung cancer progression. nm23-H1 is a metastasis suppressor gene. The molecular mechanism by which nm23-H1 suppresses the metastasis is still unclear. Here, we compared the gene expression profile of human large cell lung cancer cell line NL9980 by nm23-H1 gene silencing with that of negative control cells to comprehensively investigate nm23-H1-mediated changes in gene expression of NL9980 cells. Microarray assay revealed that expression of 733-known genes (1.9%, 733/38,500) were altered in response to nm23-H1 gene silencing, including 466 upregulated genes and 267 downregulated. real-time PCR assay of the expression changes indicated that 81.82% (45/55) of verified genes were consistent with that observed in microarray assay. The upregulated genes included MMP-1, -2, SNAI2, CXCL1, 2, 3, PAI-2, while the downregulated genes included cystatin B, TIMP-2, E-cadherin, centrin-2, all of which have been associated with tumor metastasis. Furthermore, we confirmed by Western blot that the expression of MMP-1 and -2 were significantly increased while that of cystatin B was dramatically decreased in NL9980-nm23-H1 silencing cells. The NL9980-nm23-H1 silencing cells exhibited significantly more S phase growth and invasive ability. Thus, silencing of nm23-H1 gene caused metastasis-related gene expression changes in lung cancer cells. The knockdown of nm23-H1 expression may change the lung cancer cells to a more invasive phenotype through alteration in the expression of a set of genes.
AB - Lung cancer is the leading cause of cancer death in both men and women. Tumor metastasis is an essential aspect of lung cancer progression. nm23-H1 is a metastasis suppressor gene. The molecular mechanism by which nm23-H1 suppresses the metastasis is still unclear. Here, we compared the gene expression profile of human large cell lung cancer cell line NL9980 by nm23-H1 gene silencing with that of negative control cells to comprehensively investigate nm23-H1-mediated changes in gene expression of NL9980 cells. Microarray assay revealed that expression of 733-known genes (1.9%, 733/38,500) were altered in response to nm23-H1 gene silencing, including 466 upregulated genes and 267 downregulated. real-time PCR assay of the expression changes indicated that 81.82% (45/55) of verified genes were consistent with that observed in microarray assay. The upregulated genes included MMP-1, -2, SNAI2, CXCL1, 2, 3, PAI-2, while the downregulated genes included cystatin B, TIMP-2, E-cadherin, centrin-2, all of which have been associated with tumor metastasis. Furthermore, we confirmed by Western blot that the expression of MMP-1 and -2 were significantly increased while that of cystatin B was dramatically decreased in NL9980-nm23-H1 silencing cells. The NL9980-nm23-H1 silencing cells exhibited significantly more S phase growth and invasive ability. Thus, silencing of nm23-H1 gene caused metastasis-related gene expression changes in lung cancer cells. The knockdown of nm23-H1 expression may change the lung cancer cells to a more invasive phenotype through alteration in the expression of a set of genes.
KW - Lung cancer
KW - Metastasis suppressor gene
KW - NL9980 cell line
KW - nm23-H1
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U2 - 10.1016/j.bbrc.2008.04.083
DO - 10.1016/j.bbrc.2008.04.083
M3 - Article
C2 - 18440302
AN - SCOPUS:43749094970
SN - 0006-291X
VL - 371
SP - 425
EP - 430
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -