The ras suppressor, RSU-1, enhances nerve growth factor-induced differentiation of PC12 cells and induces p21CIP expression

• Published in: Cell growth & differentiation Vol. 10; no. 8; pp. 555 - 564
• Main Authors: MASUELLI, L, ETTENBERG, S, VASATURO, F, VESTERGAARD-SYKES, K, CUTLER, M. L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.1999
• Subjects: Animals; Biological and medical sciences; Blotting, Northern; Cell Differentiation - drug effects; Cell differentiation, maturation, development, hematopoiesis; Cell Division - drug effects; Cell Line; Cell physiology; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - biosynthesis; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; Genes, ras; Growth Substances - pharmacology; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; Nerve Growth Factor - pharmacology; Neurites - drug effects; PC12 Cells; Rats; RNA, Messenger - biosynthesis; Signal Transduction - drug effects; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic - drug effects; Transfection; Cell proliferation; Rat; Adrenal glands; Induction; Rodentia; Nerve growth factor; Cell differentiation; Signal transduction; Vertebrata; Regulation(control); Cell line; Mammalia; C-Onc gene; Inhibition; Tumor suppressor gene
• ISSN: 1044-9523; 2377-0732

The Rsu-1 Ras suppressor gene was isolated based on its ability to inhibit v-Ras transformation. Using Rsu-1 transfectants of the pheochromocytoma cell line PC12, we demonstrated previously that Rsu-1 expression inhibited Jun kinase activation but enhanced Erk2 activation in response to epidermal growth factor. In the present study, the Rsu-1 PC12 transfectants were used to investigate the role of Rsu-1 in nerve growth factor (NGF)- and v-Ki-ras-mediated neuronal differentiation. NGF-induced neurite extension was enhanced, not inhibited, by the expression of Rsu-1 in PC12 cells. The activation of Erk kinase activity in response to NGF was sustained longer in the Rsu-1 transfectants compared with the vector control cells. During NGF-mediated differentiation, an increase in the expression of specific mRNAs for the early response genes Fos, cJun, and NGF1a was detected in both the vector control and Rsu-1 transfectants. The expression of the differentiation-specific genes VGF8 and SCG10 was similar in Rsu-1 transfectants compared with the vector control cells. The induction of Rsu-1 expression in these cell lines did not inhibit v-Ki-ras-induced differentiation, as measured by neurite extension. These data suggest that although Rsu-1 blocked some Ras-dependent response(s), these responses were not required for differentiation. Moreover, the induction of Rsu-1 expression in the PC12 clones resulted in growth inhibition and p21(WAF/CIP) expression. Hence, Rsu-1 expression enhances NGF-induced differentiation while inhibiting the growth of cells.