دورية أكاديمية
Role of TGF-β1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study.
| العنوان: | Role of TGF-β1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study. |
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| المؤلفون: | El-Houseini ME; Cairo University, National Cancer Institute, Department of Cancer Biology, Cairo, 11796, Egypt., Ismail A; Ain Shams University, Faculty of Medicine, Department of Surgery, Cairo, 11566, Egypt., Abdelaal AA; Ain Shams University, Faculty of Medicine, Department of Surgery, Cairo, 11566, Egypt., El-Habashy AH; Cairo University, National Cancer Institute, Department of Pathology, Cairo, 11796, Egypt., Abdallah ZF; Cairo University, National Cancer Institute, Department of Cancer Biology, Cairo, 11796, Egypt., Mohamed MZ; Medical Center of Egyptian Railways, Department of Medical Laboratory, Cairo, 11669, Egypt., El-Hadidi M; Nile University, Center of Informatics Science, Giza, 12525, Egypt., Cho WCS; Queen Elizabeth Hospital, Department of Clinical Oncology, Kowloon, Hong Kong, China., Ahmed H; GlycoMantra, Inc., Baltimore, MD 21227, USA., Al-Shafie TA; Cairo University, National Cancer Institute, Department of Cancer Biology, Cairo, 11796, Egypt. tamer.alshafie@pua.edu.eg.; Pharos University in Alexandria, Faculty of Pharmacy and Drug Manufacturing, Department of Pharmacology and Therapeutics, Alexandria, 21311, Egypt. |
| المصدر: | Biochemistry. Biokhimiia [Biochemistry (Mosc)] 2019 Aug; Vol. 84 (8), pp. 941-953. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MAIK Nauka/Interperiodica Country of Publication: United States NLM ID: 0376536 Publication Model: Print Cited Medium: Internet ISSN: 1608-3040 (Electronic) Linking ISSN: 00062979 NLM ISO Abbreviation: Biochemistry (Mosc) Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2007->: Moscow : MAIK Nauka/Interperiodica Original Publication: New York, Consultants Bureau [etc.] |
| مواضيع طبية MeSH: | Hepacivirus*, Carcinoma, Hepatocellular/*genetics , Carcinoma, Hepatocellular/*metabolism , Hepatitis C, Chronic/*genetics , Hepatitis C, Chronic/*metabolism , Liver Neoplasms/*genetics , Liver Neoplasms/*metabolism , Proto-Oncogene Proteins c-kit/*genetics , Transforming Growth Factor beta1/*pharmacology, Aged ; Carcinoma, Hepatocellular/etiology ; Cell Proliferation/drug effects ; Cells, Cultured ; Drug Resistance, Multiple, Viral ; Exons/genetics ; Female ; Gene Expression ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Humans ; Hyaluronan Receptors/metabolism ; Liver/pathology ; Liver Neoplasms/etiology ; Male ; Middle Aged ; Mutation ; Neoplastic Stem Cells/metabolism ; Thy-1 Antigens/metabolism ; Viremia |
| مستخلص: | Transforming growth factor beta (TGF-β) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-β can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-β and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-β1 on CD44 + CD90 + liver stem cells (LSCs) and C-Kit gene expression in malignant and adjacent non-malignant liver tissues excised from 32 HCC patients. The percentage of LSCs in malignant tumors was two times higher compared to their counterparts from the non-malignant tissues. When treated with increasing doses of TGF-β1, proliferation of both malignant and non-malignant LSCs was progressively suppressed, but low TGF-β1 dose failed to suppress the growth of malignant LSCs. Moreover, C-Kit exons 9 and 11 were expressed in malignant LSCs, but not in their non-malignant counterparts. Analysis of C-Kit detected mutations in exon 9 (but not in exon 11) in some malignant liver cells resulting in the changes in the amino acid sequence and dysregulation of protein structure and function. Interestingly, in malignant liver cells, mutations in exon 9 were associated with high-viremia hepatitis C virus (HCV), and expression of this exon was not suppressed by the TGF-β1 treatment at all doses. To our knowledge, this is the first report that mutations in the C-Kit gene in HCC patients are associated with high- viremia HCV. Our study emphasizes the need for investigation of the TGF-β1 level and C-Kit mutations in patients with chronic HCV for HCC prevention and better therapy management. |
| المشرفين على المادة: | 0 (CD44 protein, human) 0 (Hyaluronan Receptors) 0 (TGFB1 protein, human) 0 (Thy-1 Antigens) 0 (Transforming Growth Factor beta1) EC 2.7.10.1 (KIT protein, human) EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) |
| تواريخ الأحداث: | Date Created: 20190917 Date Completed: 20191211 Latest Revision: 20191217 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1134/S0006297919080108 |
| PMID: | 31522676 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1608-3040 |
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| DOI: | 10.1134/S0006297919080108 |