RASSF1A suppresses the c-Jun-NH2-kinase pathway and inhibits cell cycle progression.
Some oncogenes, such as activated Ras, cause the malignant transformation of lung cells. c-Jun-NH2-kinase (JNK) activation is essential for the oncogenic function of these cells. In this study, we show that RASSF1A inhibits the growth of lung cancer cells by blocking the JNK pathway. The exogenous expression of RASSF1A suppressed JNK phosphorylation, and cells stably transfected with RASSF1A showed reduced JNK and c-Jun phosphorylation and Cyclin D1 down-regulation. An in vitro kinase assay showed that the exogenous expression of RASSF1A inhibited JNK activity and that JNK activity suppression due to ectopically expressed RASSF1A was revived by RASSF1A siRNA treatment. Based on our data, we suggest that RASSF1A exerts a tumor-suppressing effect by blocking oncogene-mediated JNK activation in lung cells.
Whang
Young Mi
YM
Department of Internal Medicine and Brain Korea 21 Project for Biomedical Science, Korea University Cancer Institute, Seoul, South Korea.
Kim
Yeul Hong
YH
Kim
Jun Suk
JS
Yoo
Young Do
YD
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D000077209:Decitabine; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D016755:Proto-Oncogene Proteins c-jun; C411762:RASSF1 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D048031:JNK Mitogen-Activated Protein Kinases; D001374:Azacitidine