Activator protein-1 involved in growth inhibition by RASSF1A gene in the human gastric carcinoma cell line SGC7901.

AIM To investigate the role of Ras association domain family protein 1 isoform A (RASSF1A) in gastric tumorigenesis. METHODS Through over-expression of RASSF1A gene in the SGC7901 cell line which was induced by a lipofectamine-mediated gene transfer approach. Activator protein-1 (AP-1) DNA binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS Compared with the control clones, cells over-expressing RASSF1A exhibited significant inhibition of cell growth with G1 cell cycle arrest in vitro and in vivo. The over-expression of RASSF1A significantly inhibited AP-1 activity in SGC7901 cells (0.981+/-0.011 vs 0.354+/-0.053, P<0.001). In addition, both Western blot analysis and immunocytochemistry demonstrated that RASSF1A down-regulated the expression of c-Fos (0.975+/-0.02 vs 0.095+/-0.024, P<0.001) but not c-Jun. CONCLUSION Over-expression of RASSF1A inhibits the growth of SGC7901 cells by negatively regulating the AP-1 activity, the latter in turn negatively signals cell proliferation.

[1]  Ling Yang,et al.  Incidence and mortality of gastric cancer in China. , 2006, World journal of gastroenterology.

[2]  H. Iwao,et al.  AP-1 and colorectal cancer , 2006, InflammoPharmacology.

[3]  Hui Zheng,et al.  [The effects of hepatitis C virus core protein on biological behaviors of human hepatocytes]. , 2005, Zhonghua yi xue za zhi.

[4]  Y. Yoo,et al.  RASSF1A suppresses the c-Jun-NH2-kinase pathway and inhibits cell cycle progression. , 2005, Cancer research.

[5]  D. Xiao,et al.  Effects of transforming growth interacting factor on biological behaviors of gastric carcinoma cells. , 2005, World journal of gastroenterology.

[6]  M. Yuen,et al.  Antisense Targeting Protein Kinase C α and β1 Inhibits Gastric Carcinogenesis , 2004, Cancer Research.

[7]  J. Kwong,et al.  RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma , 2004, International journal of cancer.

[8]  K. Hoang-Xuan,et al.  Frequent epigenetic inactivation of RASSF1A and BLU genes located within the critical 3p21.3 region in gliomas , 2004, Oncogene.

[9]  M. Yuen,et al.  Antisense targeting protein kinase C alpha and beta1 inhibits gastric carcinogenesis. , 2004, Cancer research.

[10]  Julian Downward,et al.  Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. , 2003, Cancer research.

[11]  Hwoong-Yong Jung,et al.  Profile of Aberrant CpG Island Methylation along Multistep Gastric Carcinogenesis , 2003, Laboratory Investigation.

[12]  A. Protopopov,et al.  The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells. , 2002, Cancer research.

[13]  J. Minna,et al.  The RASSF1A Tumor Suppressor Blocks Cell Cycle Progression and Inhibits Cyclin D1 Accumulation , 2002, Molecular and Cellular Biology.

[14]  J. Avruch,et al.  The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1 , 2002, Oncogene.

[15]  A. Protopopov,et al.  The RASSF 1 A Tumor Suppressor Gene Is Inactivated in Prostate Tumors and Suppresses Growth of Prostate Carcinoma Cells 1 , 2002 .

[16]  S. Chi,et al.  Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation in human gastric adenocarcinoma. , 2001, Cancer research.

[17]  A. Protopopov,et al.  The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Minna,et al.  Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. , 2001, Journal of the National Cancer Institute.

[19]  M. Karin,et al.  AP-1 in cell proliferation and survival , 2001, Oncogene.

[20]  A. Bell,et al.  Ras Uses the Novel Tumor Suppressor RASSF1 as an Effector to Mediate Apoptosis* , 2000, The Journal of Biological Chemistry.

[21]  C. Vinson,et al.  Activator protein 1 transcription factors are fundamental to v-rasHa-induced changes in gene expression in neoplastic keratinocytes. , 2000, Cancer research.

[22]  Chun Xing Li,et al.  Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3 , 2000, Nature Genetics.

[23]  T Takahashi,et al.  Gains, losses, and amplifications of genomic materials in primary gastric cancers analyzed by comparative genomic hybridization , 1999, Genes, chromosomes & cancer.

[24]  C. Moskaluk,et al.  Allelotype of gastric adenocarcinoma. , 1999, Cancer research.

[25]  S. Naylor,et al.  Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes. , 1997, Advances in cancer research.