However since the simple act of placing cells in tissue culture is sufficient to activate p16INK4a gene expression and the levels of p16INK4a gene expression vary depending on the cell culture conditions[20-23], it remains unclear whether the induction of p16INK4a gene expression in cultured human primary cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. This evidence concerns the gene CDKN2A and cancer.