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Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC
Takaki Hiwasa1, Hideaki Shimada, Mari Kuboshima
1Department of Biochemistry and Genetics, Chiba University, Chuo-ku, Chiba 260-8670, Japan. hiwasa_takaki@faculty.chiba-u.jp
Abstract:
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.
Insights
A novel gene, AISEC, was identified in esophageal squamous cell carcinoma (SCC). Increased AISEC expression in SCC tissues reduces sensitivity to chemotherapy, potentially by inhibiting p53 activity.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Esophageal squamous cell carcinoma (SCC) is a significant global health concern.
- Understanding molecular mechanisms underlying SCC progression and treatment resistance is crucial.
- Serological identification of antigens by recombinant cDNA expression cloning (SEREX) can identify tumor-associated antigens.
Purpose of the Study:
- To identify novel antigens in esophageal SCC using SEREX.
- To investigate the role of identified antigens in chemosensitivity.
- To explore the molecular mechanisms by which these antigens affect drug response.
Main Methods:
- SEREX was employed using sera from esophageal SCC patients.
- A novel gene, AISEC (antigen identified by SEREX for esophageal carcinoma), was isolated.
- Quantitative RT-PCR was used to assess AISEC mRNA expression in tumor and normal tissues.
- AISEC was stably expressed in mouse fibroblasts (ras-NIH cells) to create FAISEC-3 cells.
- Chemosensitivity assays were performed on FAISEC-3 and parental ras-NIH cells using various anticancer drugs.
- Luciferase reporter assays were conducted to evaluate the effect of AISEC on p53 transactivation.
Main Results:
- AISEC mRNA expression was significantly higher in esophageal SCC tissues compared to normal tissues.
- Cells stably expressing AISEC (FAISEC-3) exhibited increased resistance to multiple anticancer drugs, including mitomycin C, ifosfamide, vincristine, camptothecin, and etoposide.
- AISEC suppressed the transactivity of p53 in a dose-dependent manner.
Conclusions:
- Esophageal SCC tissues overproduce AISEC.
- AISEC contributes to reduced chemosensitivity in esophageal SCC.
- AISEC may exert its effect by suppressing p53 transactivation, highlighting a potential therapeutic target.
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