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The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features

التفاصيل البيبلوغرافية
العنوان: The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features
المؤلفون: Hong Yi Chang, Yih Lin Tuan, Yi Wen Wang, Chien An Chu, Hsiang Lin Song, Yuh-Shyan Tsai, Yin Chien Ou, Cheng Yao Chiang, Hong Fang Song, Kun Hao Tsai, Nan Haw Chow
المصدر: Translational Oncology
Translational Oncology, Vol 14, Iss 10, Pp 101175-(2021)
سنة النشر: 2020
مصطلحات موضوعية: MAPK/ERK pathway, Cancer Research, IHC, Immunohistochemistry, INI1, Integrase Interactor 1, RCC-RF, Renal Cell Carcinoma with Rhabdoid Features, SMARCB1, MRT, Malignant Rhabdoid Tumor, PGE2, Prostaglandin E2, urologic and male genital diseases, PDGFR, Platelet-derived Growth Factor Receptors, Gefitinib, EP1, Prostaglandin E2 Receptor 1, medicine, RCC, Renal Cell Carcinoma, Epidermal growth factor receptor, NOD/SCID, Nonobese Diabetic/Severe Combined Immunodeficiency, PCR, Polymerase Chain Reaction, neoplasms, Protein kinase B, RC254-282, Original Research, ARRIVE, Animal Research Reporting In Vivo Experiments, biology, VEGF, Vascular Endothelial Growth Factor, Cell growth, business.industry, ELISA, Enzyme Linked Immunosorbent Assay, Rhabdoid differentiation, MTT, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, EMA, Epithelial Membrane Antigen, SWI/SNF, Switch/Sucrose Non-Fermentable, female genital diseases and pregnancy complications, Renal cell carcinoma, RT-PCR, Reverse Transcription Polymerase Chain Reaction, KD, Knockdown, Oncology, Erlotinib, Cancer cell, Cancer research, biology.protein, NSE, Neuron-specific Enolase, Signal transduction, business, medicine.drug
الوصف: Highlights • Inactivation of INI1 is important for renal cell carcinoma with rhabdoid features. • Down-regulation of INI1 promotes the cell proliferation and invasion in vitro. • Down-regulation of INI1 upregulates EGFR expression, PI3K/AKT and MAPK pathways. • Down-regulation of INI1 enhanced the sensitivity to everolimus or erlotinib in vitro. • Prostaglandin E2 associated signaling is an important co-targeting candidate.
Background Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. Methods Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. Results Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. Conclusion Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.
تدمد: 1936-5233
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b48aa411853196a9f39f66184a880eb
https://pubmed.ncbi.nlm.nih.gov/34243015
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....7b48aa411853196a9f39f66184a880eb
قاعدة البيانات: OpenAIRE
الوصف
تدمد:19365233