ABSTRACT
KLF13 and FGFR3 have important cellular functions and each is believed to play a role in cancer. KLF13 is a transcription factor required for the expression of several oncogenes. FGFR3 is a fibroblast growth factor receptor that initiates a signaling cascade leading to the activation of numerous cellular pathways. Here we show that KLF13 and FGFR3 are overexpressed in oral cancer cells. We also show that artificially reducing cellular levels of KLF13 and FGFR3 decreases cell proliferation and increases sensitivity to ionizing radiation. These data suggest that KLF13 and FGFR3 contribute to malignancy in oral cancer cells and may be useful biomarkers for early detection and possible targets for therapy.
Subject(s)
Carcinoma, Squamous Cell/genetics , Cell Cycle Proteins/genetics , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors/genetics , Mouth Neoplasms/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Repressor Proteins/genetics , Adult , Aged, 80 and over , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cell Cycle , Cell Differentiation , Cell Division , Cell Line, Tumor , Female , Humans , Male , Middle Aged , Mouth Neoplasms/pathology , Mouth Neoplasms/radiotherapy , Neoplasm Staging , Radiation, IonizingABSTRACT
Heterocyst differentiation in cyanobacteria is accompanied by developmentally regulated DNA rearrangements that occur within the nifD, fdxN, and hupL genes. These genetic elements are excised from the genome by site-specific recombination during the latter stages of differentiation. The nifD element is excised by the recombinase, XisA, located within the element. Our objective was to examine the XisA-mediated excision of the nifD element. To accomplish this, we observed the ability of XisA to excise substrate plasmids that contained the flanking regions of the nifD element in an E. coli host. Using PCR directed mutagenesis, nucleotides in the nifD element flanking regions in substrate plasmids were altered and the effect on recombination was determined. Results indicate that only certain nucleotides within and surrounding the direct repeats are involved in excision. In some nucleotide positions, the presence of a purine versus a pyrimidine greatly affected recombination. Our results also indicated that the site of excision and branch migration occurs in a 6 bp region within the direct repeats.
