Transcription factors and proliferative diversity of neoplastic cells

: Cancer is a multistage process with sequential steps: initiation, promotion, progression. However, the distinction between the agents that can trigger any of these processes is less clear, depending on doses, biological stage of the tissue, molecular interactions, genomic and somatic 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 leading to cellular transformation, in lower dosage are able to alter nuclear proteins which in turn favor the action of other agents triggering the initiation process. Transcription factors (TF) are nuclear proteins with particular structural configurations for their interaction with DNA. There are families of TF with specificity for certain nucleotide sequences called "response elements". The association TF-DNA response elements modulate the genomic transcription and synthesis of proteins, many of which are related to cellular proliferation. The transcriptional message can also be influenced by TF protein-protein interactions, besides their association with the response elements. This "cross-talk" or "side regulation" becomes an important genomic regulatory mechanism. Certain biochemical signals acting on particular proteins (receptors, enzymes) can then trigger biological effects attributable to other proteins. Another transcriptional regulatory mechanism is the cytoplasm-nucleus shuttling of TF according to the cellular replication rhythm and other metabolic cellular requirements. These recent advances open new vistas for the pharmacological attack to the proliferative diversity of neoplastic cells.