Carcinogenesis, Vol. 21, No. 11, 2073-2077,
November 2000
© 2000 Oxford University Press
Carcinogenesis |
Role of the ß isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation
Department of Medical Genetics and Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University and
1 Department of Developmental Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the ß isoform of the 14-3-3 proteins (14-3-3 ß) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Overexpression of 14-3-3 ß in NIH 3T3 cells stimulated cell growth and supported anchorage-independent growth in soft agar medium and tumor formation in nude mice. To elucidate the molecular mechanisms of 14-3-3 ß-mediated NIH 3T3 transformation, we examined the activity of mitogen-activated protein kinase (MAPK) after serum stimulation. Overexpression of 14-3-3 ß augmented MAPK activity after serum stimulation, and MAPK activity correlated well with the amount of 14-3-3 ß expression. The colony-forming ability of NIH 3T3 cells overexpressing 14-3-3 ß in soft agar medium was efficiently abolished by exogenous expression of a dominant-negative mutant of MEK1 and 14-3-3 ß physically interacted with Raf-1 in these cells. These findings indicate that 14-3-3 ß has oncogenic potential, mainly through enhancement of Raf-1 activation and resultant augmentation of signaling in the MAPK cascade.
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