E1AF/PEA3 reduces the invasiveness of SiHa cervical cancer cells by activating serine proteinase inhibitor squamous cell carcinoma antigen.
E1AF/PEA3, a member of the Ets family of transcription factors, is associated with the malignant characteristics of cancer cells. The initial aim of our study was to test whether the invasiveness of SiHa cervical cancer cells could be diminished by transfection with antisense E1AF. Using an in vitro invasion assay in which cells penetrate a layer of Matrigel, we found that this was not the case; indeed, the invasiveness of the transfectants was enhanced. To better understand the mechanism of this enhancement, we used the cDNA microarray technique to search for genes whose expression was altered in the antisense E1AF-transfected SiHa cells. Among several genes affected, we found that expression of squamous cell carcinoma antigen (SCCA), a member of the ovalbumin serine proteinase inhibitor family, was significantly reduced. Forced expression of E1AF enabled activation of SCCA expression, and Luciferase reporter assays revealed that E1AF activates the SCCA promoter. Introduction of antisense SCCA into SiHa cells inhibited production of SCCA protein and markedly increased the invasiveness of the cells. Taken together, these results suggest that E1AF suppresses the invasiveness of SiHa cervical cancer cells through transcriptional activation of the SCCA serine proteinase inhibitor gene.
Iwasaki
Masahiro
M
Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo 060-8543, Japan.
Nishikawa
Akira
A
Akutagawa
Noriyuki
N
Fujimoto
Takashi
T
Teramoto
Mizue
M
Sakaguchi
Yuko
Y
Kato
Hiroshi
H
Ito
Miyuki
M
Yoshida
Koichi
K
Kudo
Ryuichi
R
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002477:Cells; D003094:Collagen / Q000737:chemistry; D016373:DNA, Antisense / Q000494:pharmacology; D004338:Drug Combinations; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008156:Luciferases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D017500:Adenovirus E1A Proteins; D000951:Antigens, Neoplasm; D016373:DNA, Antisense; D004338:Drug Combinations; C079853:ETV4 protein, human; D007797:Laminin; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; C059485:matrigel; D003094:Collagen; D008156:Luciferases