In vivo identification of novel target genes in colorectal adenocarcinoma by the cDNA-AFLP technique

Backgrounds: Homeobox-containing genes are composed of a group of regulatory genesencoding transcription factors involved in the control of developmental processes. Thehomeodomain proteins could activate or repress the expression of downstream target genes.These proteins have been reported to regulate various embryonic developmental processes suchas axis formation, limb development, and organogenesis. A number of gene alterations inhomeobox genes have been established to be involved in diseases such as neuroblastoma,leukemia, and cancer. This study was conducted to in vivo identify the potential target gene(s) ofTGIF۲LX in colorectal adenocarcinoma.Materials and Methods: A human colorectal adenocarcinoma cell line, SW۴۸, was transfectedwith the recombinant pEGFPN۱-TGIF۲LX. The cells were injected subcutaneously into theflank of the three groups of ۶-week-old female athymic C۵۶BL/۶ nude mice (n = ۶ per group).The transcript profiles in the developed tumors were investigated using the cDNA amplifiedfragment length polymorphism (cDNA-AFLP) technique.Results: The real-time RT-PCR and DNA sequencing data for the identified genes indicated thatthe N-terminal domain-interacting receptor ۱ (Nir۱) gene was suppressed whereas Nir۲ andfragile histidine triad (FHIT) genes were upregulated followed by the overexpression ofTGIF۲LX gene.Conclusion: Downregulation of Nir۱ and upregulation of Nir۲ and FHIT genes due to theoverexpression of TGIF۲LX suggests that the gene plays an important role as a suppressor incolorectal adenocarcinoma.

کلیدواژه ها:

Target genes ، Colorectal adenocarcinoma ، Homeobox ، cDNA-AFLP