Antisense E1AF transfection restrains oral cancer invasion by reducing matrix metalloproteinase activities.
E1AF is a newly identified human ets-family transcription factor. We have reported that E1AF can up-regulate transcription of matrix metalloproteinase (MMP) genes and confers invasive phenotype on human cancer cells. HSC3 is an oral squamous-cell-carcinoma-derived cell line, and it manifests high levels of E1AF and MMP-1 and -9 gene expression that are associated with invasive potential. We reconstructed an E1AF antisense expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express E1AF antisense RNA. HSC3AS showed decreasing mRNA and protein levels of MMP-1, -3, and -9. Moreover, HSC3AS showed lower invasive potential in vitro three-dimensional raft culture and in vivo implantation into nude mice. These results imply that transfection of antisense E1AF inhibits tumor invasion by down-regulating MMP genes.
Hida
K
K
Department of Oral Surgery, Hokkaido University School of Dentistry, Japan.
Shindoh
M
M
Yasuda
M
M
Hanzawa
M
M
Funaoka
K
K
Kohgo
T
T
Amemiya
A
A
Totsuka
Y
Y
Yoshida
K
K
Fujinaga
K
K
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016372:RNA, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1