Suppression of PTEN Expression Is Essential for Antiapoptosis and Cellular Transformation by Oncogenic Ras -- Vasudevan et al. 67 (21): 10343 -- Cancer Research
Rangnekar, Branch of Radiation Medicine, University of Kentucky, Combs Proof Building, Interval 309, 800 Rose Street, Lexington, KY 40536. Ras is one of the most commonly mutated oncogenes in the array of human cancers. The mechanism by which Ras induces cellular transformation is, however, not fully elucidated.
June + + cells undergo cellular transformation by oncogenic Ras, and restoration of wild-type PTEN, on the other hand not a phosphate-defective mutant of PTEN, induces apoptosis in these cells. Conversely, in Jun - - cells, oncogenic Ras neither suppresses PTEN nor causes transformation, on the contrary rather it induces PTEN-dependent apoptosis. An apoptotic response to oncogenic Ras in Jun - - cells can be prevented by suppressing PTEN expression.
These findings imply that oncogenic Ras suppresses the apoptotic gene PTEN via the Raf-MEK-ERK-c-Jun road to induce antiapoptosis and cellular transformation. Together, our findings describe a tale molecular interface between the oncogenic and tumour suppressor pathways that regulates cellular transformation and survival.
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