Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC.
We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.
Hiwasa
Takaki
T
Department of Biochemistry and Genetics, Chiba University, Chuo-ku, Chiba 260-8670, Japan. hiwasa_takaki@faculty.chiba-u.jp
Shimada
Hideaki
H
Kuboshima
Mari
M
Shiratori
Tooru
T
Kagaya
Akiko
A
Nabeya
Yoshihiro
Y
Sugano
Sumio
S
Ochiai
Takenori
T
Matsubara
Hisahiro
H
Takiguchi
Masaki
M
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53