دورية أكاديمية
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Expression and roles of system L amino acid transporters in human embryonal carcinoma cells.

التفاصيل البيبلوغرافية
العنوان: Expression and roles of system L amino acid transporters in human embryonal carcinoma cells.
المؤلفون: Chatsirisupachai K; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Kitdumrongthum S; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand., Panvongsa W; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand., Janpipatkul K; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Worakitchanon W; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Lertjintanakit S; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand., Wongtrakoongate P; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, Thailand., Chairoungdua A; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand.; Excellent Center for Drug Discovery (ECDD), Mahidol University, Bangkok, Thailand.
المصدر: Andrology [Andrology] 2020 Nov; Vol. 8 (6), pp. 1844-1858. Date of Electronic Publication: 2020 Aug 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101585129 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-2927 (Electronic) Linking ISSN: 20472919 NLM ISO Abbreviation: Andrology Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Wiley-Blackwell, 2013-
مواضيع طبية MeSH: Amino Acid Transport System L/*biosynthesis , Amino Acid Transport System L/*metabolism , Carcinoma, Embryonal/*pathology , Embryonal Carcinoma Stem Cells/*metabolism , Testicular Neoplasms/*pathology, Adaptor Proteins, Signal Transducing/biosynthesis ; Antineoplastic Agents/pharmacology ; Carcinogenesis/pathology ; Carcinoma, Embryonal/drug therapy ; Cell Line, Tumor ; Cell Proliferation/physiology ; Cell Survival/physiology ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm/genetics ; Fusion Regulatory Protein 1, Heavy Chain/biosynthesis ; Humans ; Large Neutral Amino Acid-Transporter 1/biosynthesis ; Male ; Testicular Neoplasms/drug therapy
مستخلص: Background: Testicular germ cell tumors (TGCTs) are the most common malignant cancer in young men. Although TGCTs are generally responsive to platinum-based chemotherapy particularly cisplatin, acquired resistance in patients with metastasis still occurs resulting in poor prognosis. Specifically, differentiation of embryonal carcinoma (EC) cells, the stem cells of TGCTs, can lead to the reduction of cisplatin responsiveness. Therefore, novel therapeutic strategies for TGCTs are needed. System L amino acid transporters have been reported to be up-regulated and to play an important role in tumorigenesis. However, expression and role of system L amino acid transporters in TGCTs remain elusive.
Materials and Methods: Expression of system L amino acid transporters was analyzed in TGCT samples from The Cancer Genome Atlas (TCGA). Expression of LAT1, LAT2, and 4F2hc was examined in human embryonal carcinoma cell line NTERA2. Roles of system L amino acid transporters on NTERA2 cell survival, cell proliferation, pluripotency, and cisplatin sensitivity were evaluated.
Results: Based upon TCGA datasets, we found that two isoforms of system L (LAT1 and LAT2) and their chaperone protein 4F2hc are highly expressed in EC samples compared with other groups. Treatment with the system L inhibitor BCH significantly suppressed leucine uptake into the pluripotent EC cell line NTERA2. The malignant phenotypes including cell viability, cell proliferation, and clonal ability were decreased following BCH treatment. Nonetheless, system L inhibition did not alter expression of stemness genes in NTERA2 cells. After NTERA2 differentiation, expressions of LAT1 and LAT2 were decreased. Finally, co-administration of BCH enhanced cisplatin sensitivity in both undifferentiated and differentiated cells. These effects were associated with the reduction in p70S6K phosphorylation.
Conclusion: Taken together, these results shed light on the roles of system L amino acid transporters in TGCTs. Therefore, system L amino acid transporters could provide novel therapeutic targets for treatment against TGCTs.
(© 2020 American Society of Andrology and European Academy of Andrology.)
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فهرسة مساهمة: Keywords: 4F2hc; LAT1; embryonal carcinoma cells; system L amino acid transporters; testicular germ cell tumors
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Amino Acid Transport System L)
0 (Antineoplastic Agents)
0 (Fusion Regulatory Protein 1, Heavy Chain)
0 (LAT2 protein, human)
0 (Large Neutral Amino Acid-Transporter 1)
0 (SLC3A2 protein, human)
0 (SLC7A5 protein, human)
Q20Q21Q62J (Cisplatin)
تواريخ الأحداث: Date Created: 20200803 Date Completed: 20211006 Latest Revision: 20211006
رمز التحديث: 20231215
DOI: 10.1111/andr.12880
PMID: 32741077
قاعدة البيانات: MEDLINE
الوصف
تدمد:2047-2927
DOI:10.1111/andr.12880