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


CONCLUSIONS
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.
Deng
Zheng-Hao
ZH
Department of Pathology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan Province, China.
Wen
Ji-Fang
JF
Li
Jing-He
JH
Xiao
De-Sheng
DS
Zhou
Jian-Hua
JH
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D016760:Proto-Oncogene Proteins c-fos; C411762:RASSF1 protein, human; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins