Factor-κb Regulates Cyclooxygenase-2 Expression and Cell Proliferation in Human Colorectal Carcinoma Tissue

NF-κB is an inducible transcription factor that mediates signal transduction between the cytoplasm and nucleus in many cell types [1] and controls the expression of numerous genes involved in cell growth, differentiation, regulation of apoptosis, cytokine production, and neoplastic transformation [2]. It is a member of the Rel family, which includes NF-κB1 (p50), NF-κB2 (p52), RelA (p65), RelB, c-Rel and Drosophila morphogen dorsal gene product [3]. They have a high level of sequence homology within their NH2-terminal 300 amino acids, the Rel homology domain [4]. The p50 and p52 can interact with the RelA proteins to form all possible homoand heterodimer combinations. The most common dimer is the RelA (p65)/NF-κB1 (p50) heterodimer, i.e., NF-κB. In most unstimulated cells, Rel/NF-κB proteins are sequestered in the cytoplasm and are complexed with specific inhibitor proteins called IκB that render the Rel/NFκB proteins inactive [4]. Stimulation by a variety of pathogenic inducers such as viruses, mitogens, bacteria, agents providing oxygen radicals, and inflammatory cytokines, leads to phosphorylation and degradation of IκB and allows translocation of Rel/NF-κB to the nucleus, resulting in expression of target genes [5]. Several investigators have reported constitutive activation of NF-κB in various types of human tumor cell lines, including those of lymphoid origin such as Hodgkin/Reed Sternberg cells [6], T-cell lymphoma Hut