RB1 and neoplasm: In non-transformed cells, MDM2 and p53 proteins are weakly expressed, while MDM2 upregulation in cancer cells can be, in many cases, induced not only by p53-independent factors but also caused by the induction of p53-independent pro-survival mechanisms, including inhibition of tumour suppressor activity of the Rb protein or E2F transcription factor 1 [37].