TRANSCRIPTION FACTORS AND PROLIFERATIVE D IVERSITY OF NEOPLASTIC-CELLS

Cancer is a multistage process with sequential steps: initiation, prom otion, progression. However, the distinction between the agents that c an trigger any of these processes is less clear, depending on doses, b iological stage of the tissue, molecular interactions, genomic and som atic mutation, etc. Thus, steroid receptors, classically considered as promoters, could be acting as initiators under different alterations. On the other hand, chemical carcinogens that can produce DNA damage l eading to cellular transformation, in lower dosage are able to alter n uclear proteins which in turn favor the action of other agents trigger ing the initiation process. Transcription factors (TF) are nuclear pro teins with particular structural configurations for their interaction with DNA. There are families of TF with specificity for certain nucleo tide sequences called ''response elements''. The association TF-DNA re sponse elements modulate the genomic transcription and synthesis of pr oteins, many of which are related to cellular proliferation. The trans criptional message can also be influenced by TF protein-protein intera ctions, besides their association with the response elements. This ''c ross-talk'' or ''side regulation'' becomes an important genomic regula tory mechanism. Certain biochemical signals acting on particular prote ins (receptors, enzymes) can then trigger biological effects attributa ble to other proteins. Another transcriptional regulatory mechanism is the cytoplasm-nucleus shuttling of TF according to the cellular repli cation rythm and other metabolic cellular requirements. These recent a dvances open new vistas for the pharmacological attack to the prolifer ative diversity of neoplastic cells.