Simultaneous knockdown of BRAF and expression of INK4A in melanoma cells leads to potent growth inhibition and apoptosis

摘要: Abnormal BRAF and p16INK4A co-exist in 60% of melanomas. mutation also occurs 80% benign nevi where it turns-on resulting proliferative senescence; loss removes the inhibitory block leading to melanoma development. Since only melanomas with wild-type have amplified CDK4 cyclin D1 genes, p16INK4A-CDK4/6-cyclin D pathway is viewed as linearly downstream BRAF. Thus, co-occurrence aberrant INK4A may be remnant changes during formation without functional significance. To explore this notion, we simultaneously knocked down (via siRNA) expressed cDNA cells observed enhanced growth inhibition. Notably, although each alone had no statistically significant effect on apoptosis, co-expression siRNA caused potent which was associated up-regulation BIM down-regulation BCL2. Our results suggest that cooperate promote proliferation survival cells.