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.