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

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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