RASSF1A suppresses the c-jun-NH2-kinase pathway and inhibits cell cycle progression

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 9; pp. 3682 - 3690
• Main Authors: Whang, Young Mi, Kim, Yeul Hong, Kim, Jun Suk, Yoo, Young Do
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.05.2005
• Subjects: Antineoplastic agents; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Biological and medical sciences; Cell Growth Processes - physiology; Cell Line, Tumor; G1 Phase - physiology; Humans; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical sciences; Pharmacology. Drug treatments; Phosphorylation; Proto-Oncogene Proteins c-jun - metabolism; RNA, Small Interfering - genetics; Transfection; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Tumors; Signal transduction; Enzyme; Kinase; Transferases; C-Onc gene; Cell cycle; Mitogen-activated protein kinase; Inhibitor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-04-2792

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.