Polo-like kinase and survivin are esophageal tumor-specific promoters.
For developing successful cancer gene therapy strategies, tumor-specific gene delivery is essential. In this study, we used esophageal cancer (EC) cells to identify and evaluate esophageal tumor-specific gene promoters. Four genes (polo-like kinase-1/PLK, survivin/BIRC5, karyopherin alpha 2/KPNA2, and pituitary tumor transforming gene protein 1/PTTG1) were identified by a microarray analysis as highly expressed in EC cell lines vs. five normal organ tissues (liver, lung, kidney, brain, and heart). By quantitative RT-PCR, the average mRNA expression levels of these four genes in 20 primary ECs were 2.7-fold (PLK), 6.1-fold (survivin), 2.6-fold (KPNA2), and 2.4-fold (PTTG1) higher than that of each gene in 24 different normal organs. By dual luciferase assay, the promoter activity of PLK and survivin in EC cell lines was 18.9-fold and 28.5-fold higher, respectively, than in normal lung and renal cells. The promoters of PLK and survivin could be useful tools for developing EC-specific gene therapy vectors.
Sato
Fumiaki
F
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. fsato@som.umaryland.edu
Abraham
John M
JM
Yin
Jing
J
Kan
Takatsugu
T
Ito
Tetsuo
T
Mori
Yuriko
Y
Hamilton
James P
JP
Jin
Zhe
Z
Cheng
Yulan
Y
Paun
Bogdan
B
Berki
Agnes T
AT
Wang
Suna
S
Shimada
Yutaka
Y
Meltzer
Stephen J
SJ
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D000077022:Survivin; D028901:alpha Karyopherins; D000097869:Polo-Like Kinase 1
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D064249:Securin; D000077022:Survivin; D028901:alpha Karyopherins; D000097869:Polo-Like Kinase 1; C107489:BIRC5 protein, human; C490630:KPNA2 protein, human; C578002:pituitary tumor-transforming protein 1, human