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肺癌细胞中UbcH10、p53和表皮生长因子受体(EGFR)之间的相互联系及其与治疗反应的关系

The Interconnection Between UbcH10, p53, and EGFR in Lung Cancer Cells and Their Involvement in Treatment Response.

作者信息

Quintavalle Cristina, Malapelle Umberto, De Martino Marco, Rocco Danilo, Fusco Alfredo, Pepe Francesco, Bellevicine Claudio, Esposito Francesco, Pallante Pierlorenzo

机构信息

Institute of Endotypes in Oncology, Metabolism and Immunology (IEOMI) "G. Salvatore", National Research Council (CNR), S. Pansini 5, 80131 Naples, Italy.

Department of Public Health, University of Naples "Federico II", S. Pansini 5, 80131 Naples, Italy.

出版信息

Genes (Basel). 2025 Mar 30;16(4):404. doi: 10.3390/genes16040404.

Abstract

: The UbcH10 protein plays an important role in a variety of human malignancies, including thyroid, breast, ovarian, and colorectal carcinomas. It has been previously reported that UbcH10 is overexpressed in non-small cell lung cancer (NSCLC) compared to normal lungs and that its expression is directly and inversely correlated with the mutational status of and , respectively. : We transfected lung cancer cells with wild-type and mutant forms of , modulated the expression of UbcH10 and p53, and treated these cells with tyrosine kinase inhibitor (TKI) erlotinib. Using Western blotting, we evaluated the expression of UbcH10 induced by EGFR and p53. Finally, we employed immunohistochemistry to assess the levels of UbcH10 expression in a subset of NSCLC patients receiving TKI therapy. : We reported a possible modulation of UbcH10 expression by the overexpression of wild-type and mutant EGFR in H460 lung cancer cells, potentially through p53. The enforced expression of UbcH10 in cells transfected with mutant suggested a potential increase in resistance to erlotinib treatment. Finally, immunohistochemical analysis of samples from NSCLC patients with mutant indicated a possible connection between UbcH10 expression levels and progression-free survival. : In NSCLC, UbcH10 may play a role in the regulation of TKI response via a molecular pathway potentially involving p53 and EGFR. However, further research is needed to fully understand this mechanism.

摘要

UbcH10蛋白在多种人类恶性肿瘤中发挥重要作用,包括甲状腺癌、乳腺癌、卵巢癌和结直肠癌。此前有报道称,与正常肺组织相比,UbcH10在非小细胞肺癌(NSCLC)中过表达,并且其表达分别与 和 的突变状态呈正相关和负相关。我们用野生型和突变型 的形式转染肺癌细胞,调节UbcH10和p53的表达,并用酪氨酸激酶抑制剂(TKI)厄洛替尼处理这些细胞。通过蛋白质免疫印迹法,我们评估了由表皮生长因子受体(EGFR)和p53诱导的UbcH10的表达。最后,我们采用免疫组织化学方法评估了接受TKI治疗的一部分NSCLC患者中UbcH10的表达水平。我们报道了在H460肺癌细胞中,野生型和突变型EGFR的过表达可能通过p53调节UbcH10的表达。在转染了突变型 的细胞中强制表达UbcH10表明对厄洛替尼治疗的耐药性可能增加。最后,对具有突变型 的NSCLC患者样本的免疫组织化学分析表明UbcH10表达水平与无进展生存期之间可能存在联系。在NSCLC中,UbcH10可能通过一条可能涉及p53和EGFR的分子途径在TKI反应的调节中发挥作用。然而,需要进一步研究以充分理解这一机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c87/12026858/c73e870f1186/genes-16-00404-g001.jpg

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