[Genetic diagnosis of colorectal cancer].
Accumulating evidences that carcinogenesis requires multiple gene alterations of oncogenes and tumor suppressor genes have recently emerged. In addition, genes related to invasion and metastasis are also important in understanding development of colorectal cancer. In this study, clinical significance and application of tumor suppressor genes and invasion related genes such as APC (adenomatous polyposis coli), DCC (deleted in colorectal carcinoma) tumor suppressor genes and invasion related gene, matrilysin were studied. In the mouse tumor induced by mutagen contained in cooked food, PhIP (2-amino-1-methyl-6- phenylimidazo [4,5-b] pyridine), nonsense mutations of APC gene that is similar to human colorectal cancer have been observed. These results suggested the quite interesting issue of mutagen contained in daily food having etiological role of colorectal cancer. DCC gene alteration, decreased expression of DCC mRNA was detected in 60% of advanced colorectal cancer. In all cases with liver metastasis, DCC expression was absent or markedly decreased, a finding that detection of DCC expression have an clinical importance that predicts metastatic potential of colorectal cancer. Matrilysin, the member of MMPs (matrix metalloproteinases) which degrade matrix components such as type IV collagen, laminin or fibronectin. In most of colorectal cancer, matrilysin was overexpressed in tumor cells. Matrilysin-transfected colorectal cancer cells showed more invasive ability in vitro and gained metastatic potential in SCID mice. Suppression of matrilysin expression by treated with all-trans retinoic acid (ATRA) or introduction of anti-sense matrilysin decreased the invasive ability in vitro. This result suggests that matrilysin plays an important role in invasion and metastasis and have a possibility of new anti-invasion therapy.
Itoh
F
F
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Imai
K
K
D000818:Animals; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D017491:Genes, APC; D016163:Genes, DCC; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics
D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7