Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated Ki-ras via AP-1 activation in SW1417 colon cancer cells.
The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.
Yamamoto
H
H
First Department of Internal Medicine, Sapporo Medical University, Japan.
Itoh
F
F
Senota
A
A
Adachi
Y
Y
Yoshimoto
M
M
Endoh
T
T
Hinoda
Y
Y
Yachi
A
A
Imai
K
K
D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000502:physiology
D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D002795:Choline O-Acetyltransferase; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7