Zinc Finger Transcription Factor Gklf As A Tumor Suppressor Gene Function

Malignant tumor is one of the leading diseases that endanger the life of human beings. Aberrant activation of proto-oncogenes and inactivation of tumor suppressor genes occur frequently in the initiation, progression of malignant tumors, which could further lead to abnormities of signal transduction in cells.Each cell needs biological signals to maintain its life cycle. It is well known that the functions of most of these signals are carried out by controlling the transcription of a set of target genes. For cancer cell, the network of signal transduction and the control of gene expression are usually more complex than normal cells, because of the malignant characters. The activity of transcription factor is critical for the regulation of transcription of genes. Thus, it will benefit us greatly to give more concerns and study extensively on transcription factor(s). This will not only give better elucidation on the mechanisms of signal transduction, but also further our understanding on the nature of malignant tumor.GKLF (Gut-enriched Kruppel-Like Factor) was identified almost at the same time in 1996 by two groups leaded by Yang and de Crombrugghe independently. The name came from the observations that its expression was enriched at the epithelium of gut and its high homology with members of Kruppel-like factor family which characterized by the three C₂H₂ zinc fingers at the carboxyl terminal. The human GKLF gene localized to chromosome 9q31 and encoded a protein which consists of 470 amino acids. Like other members of the family, there are three C₂H₂ zinc fingers at the carboxyl terminal of GKLF protein which mainly function as DNA binding domain. Besides this domain, GKLF also have transactivation domain and transrepression domain, which make it to be a dual-function transcription factor.Expression of GKLF during the development of animals suggested that it might participate in the control of cell proliferation and differentiation. It has been reported that GKLF was downregulated in colon cancer, bladder caner and gastric cancer but upregulated in breast cancer. Ectopic expression of GKLF in cell lines of colon cancer, bladder caner or gastric cancer could inhibit cell proliferation and induce cell apoptosis. However, overexpression of GKLF in breast cancer cell line will promote cell malignant transformation.