Receptor tyrosine kinase KIT may regulate expression of genes involved in spontaneous regression of neuroblastoma

An important feature of neuroblastoma is its ability to spontaneously regress or differentiate into a benign tumor at all stages of the disease; however, the mechanisms underlying these processes are not well understood. We determined the effect of the receptor tyrosine kinase KIT on the expression of several genes that may be involved in the tumor spontaneous regression. The downregulation of KIT through RNA interference in the SH-SY5Y neuroblastoma cells led to the decreased expression of the nerve growth factor (NGF) receptor, which may contribute to a loss of sensitivity of the cells to NGF, and the overexpression of another receptor TrkA that stimulates cell differentiation and apoptosis depending on the presence of NGF. In addition, there is the upregulation of genes that stimulate the recognition of malignant cells by the immune system, such as genes of major histocompatibility complex class-I HLA-B and HLA-C, and interferon-γ receptor genes IFNGR1 and IFNGR2. Thus, KIT may affect the sensitivity of neuroblastoma cells to neurotrophins and components of the immune system, i.e., up to two factors involved in the spontaneous regression of neuroblastoma.