Polyamine-dependent expression of the matrix metalloproteinase matrilysin in a human colon cancer-derived cell line.
Matrilysin, which is a member of the matrix metalloproteinase family and is implicated in colon cancer invasion, is expressed in human colon adenocarcinoma-derived SW1116 cells. We investigated the effect of alpha-difluoromethylornithine (DFMO) on matrilysin expression in this cell line because others have shown that DFMO can inhibit invasion and carcinogenesis in epithelial tissues, including the colon, in experimental models. DFMO reduced extracellular levels of matrilysin protein after 4 d of treatment. Intracellular levels of matrilysin protein were minimally affected by DFMO treatment. The decrease in extracellular matrilysin protein levels caused by DFMO was not a consequence of lowered steady-state levels of matrilysin mRNA. After 4 d of exposure, the amount of this transcript was higher in DFMO-treated cells than in untreated cultures, whereas the mRNA stabilities were similar. These data show that polyamine depletion by DFMO can suppress the expression of matrilysin, a gene product thought to be involved in tumor invasion. The decrease in extracellular matrilysin protein caused by DFMO treatment appears to be due to a posttranscriptional mechanism, although transcription of this gene also seems to be affected by polyamines in SW1116 cells.
Wallon
U M
UM
Department of Radiation Oncology, University of Arizona Health Sciences Center, Tucson 85724.
Shassetz
L R
LR
Cress
A E
AE
Bowden
G T
GT
Gerner
E W
EW
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000918:Antibody Specificity; D015317:Biogenic Polyamines / Q000378:metabolism / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000518:Eflornithine / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D000518:Eflornithine