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Akira Kikuchi



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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-57 - The Role of Arl4c in the Carcinogenesis Process of Lung Adenocarcinoma (Now Available) (ID 2884)

      10:15 - 18:15  |  Author(s): Akira Kikuchi

      • Abstract
      • Slides

      Background

      The aberrant activations of EGF / Ras and Wnt / β-catenin signaling are known to be closely involved in carcinogenesis and malignant transformation of various cancers, but the mechanism in carcinogenesis is unknown in detail. The expression of ADP-ribosylation factor (ARF) -like 4c (Arl4c) is induced by the EGF / Ras and the Wnt / β-catenin signalling, and immunohistochemical analyses of tissue specimens obtained from lung adenocarcinoma patients revealed that Arl4c was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor lesions. In addition, the positivity of Arl4c expression was not correlated with the tumor’s T grade or N grade. These findings suggest that this protein may be involved in the process of carcinogenesis of lung adenocarcinoma. In this study, we analyzed the role of Arl4c in the carcinogenesis process of lung adenocarcinoma, using immunohistochemical analyses of tissue specimens, and normal human small airway epithelial cell (SAEC) cancer model in vitro.

      Method

      Using the specimens resected from patients who performed lung resection, Arl4c expression was immunohistochemically examined in Atypical Adenomatous Hyperplasia (AAH), which is a pre-cancerous stage, and relationships between Arl4c expression and clinicopathological characteristics were analyzed. In vitro, to establish an immortalized SAEC, we introduced hTERT, CDK4 and DN-p53 to SAEC (SAEC-Triple) with retroviral vector plasmids. Then, we established cell lines stably expressing Arl4c. Using these cells, we assessed the proliferative capacity in a two-dimensional (2D) plastic dish culture and 3D Matrigel culture. In addition, to assess the cell tumorigenic ability , we performed the 2D clonogenic colony formation assay.

      Result

      The expression of Arl4c was observed in 22 of 27 patients (81%) with AAH, while Arl4c-positive cells were never observed in the alveolar epithelium of non-AAH region. No significant difference in clinicopathologic characteristics between Arl4c positive and Arl4c negative groups. In vitro, Alr4c were transfected into SAEC-Triple and confirmed the expression of these proteins by the western blotting. In 2D culture, there was no significant difference between the cell proliferation capacity of SAEC-Triple with Arl4c and that of SAEC-Triple with control vector. In contrast, when SAEC-Triple were grown in 3D Matrigel, stable expression of Arl4c was remarkably increased sphere areas. In a 2D clonogenic colony formation assay, the number of colonies was much higher in SAEC-Triple with Arl4c compared to SAEC-Triple with control vector (P < 0.05). Consistent with these findings, Phosphorylation of Erk1/2 was significantly increased in SAEC-Triple with Arl4c compared with cells expressing control.

      Conclusion

      Arl4c expression in AAH lesion indicated that Arl4c involved in the processes of lung carcinogenesis. Arl4c promotes proliferative capacity by activating Phosphorylation of Erk1/2.

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