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建立一株裸鼠口腔癌细胞系及其与该癌相关的遗传学改变的鉴定。

Establishment of a Null Murine Oral Carcinoma Cell Line and the Identification of Genetic Alterations Associated with This Carcinoma.

机构信息

Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan.

Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan.

出版信息

Int J Mol Sci. 2020 Dec 8;21(24):9354. doi: 10.3390/ijms21249354.

Abstract

Head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC), ranks sixth in cancer incidence worldwide. To generate OSCC cells lines from human or murine tumors, greatly facilitates investigations into OSCC. This study describes the establishing of a mouse palatal carcinoma cell line (designated MPC-1) from a spontaneous tumor present in a heterozygous gene loss C57BL/6 mouse. A MPC-1-GFP cell subclone was then generated by lentivirus infection resulting in stable expression of green fluorescent protein. Assays indicated that MPC-1 was a null polygonal cell that was positive for keratinocyte markers; it also expressed vimentin and showed a loss of E-cadherin expression. Despite that MPC-1 having strong proliferation and colony formation capabilities, the potential for anchorage independent growth and tumorigenesis was almost absent. Like other murine MOC-L and MTCQ cell line series we have previously established, MPC-1 also expresses a range of stemness markers, various oncogenic proteins, and a number of immune checkpoint proteins at high levels. However, the synergistic effects of the CDK4/6 inhibitor palbociclib on other therapeutic drugs were not observed with MPC-1. Whole exon sequencing revealed that there were high rates of non-synonymous mutations in MPC-1 affecting various genes, including , , , , , , , , and , which are similar to that the mutations present in a panel of chemical carcinogenesis-related murine tongue carcinoma cell lines. Analysis has highlighted the dis-regulation of , , , , and in human HNSCC as indicated by the TCGA and GEO OSCC databases. expression has also been associated with patient survival. This study describes the establishment and characterization of the MPC-1 cell line and this new cell model should help to advance genetic research into oral cancer.

摘要

头颈部鳞状细胞癌(HNSCC),包括口腔鳞状细胞癌(OSCC),在全球癌症发病率中排名第六。从人类或鼠肿瘤中生成 OSCC 细胞系,极大地促进了对 OSCC 的研究。本研究描述了从杂合性基因缺失的 C57BL/6 小鼠中自发肿瘤建立的鼠腭癌细胞系(命名为 MPC-1)。然后通过慢病毒感染生成 MPC-1-GFP 细胞亚克隆,导致绿色荧光蛋白的稳定表达。分析表明,MPC-1 是一种呈多边形的 缺失细胞,角蛋白标志物阳性;它还表达波形蛋白,E-钙粘蛋白表达缺失。尽管 MPC-1 具有很强的增殖和集落形成能力,但几乎没有锚定非依赖性生长和致瘤性的潜力。与我们之前建立的其他鼠 MOC-L 和 MTCQ 细胞系系列一样,MPC-1 也高水平表达一系列干性标志物、各种致癌蛋白和许多免疫检查点蛋白。然而,在 MPC-1 中未观察到 CDK4/6 抑制剂 palbociclib 与其他治疗药物的协同作用。全外显子测序显示,MPC-1 中存在影响各种基因的非同义突变的高突变率,包括、、、、、、、和,与化学致癌相关的鼠舌癌细胞系面板中的突变相似。分析强调了 TCGA 和 GEO OSCC 数据库中人类 HNSCC 中、、、和的失调。表达与患者生存有关。本研究描述了 MPC-1 细胞系的建立和特性,这个新的细胞模型应该有助于推进口腔癌的遗传研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c33a/7764333/ecf9b9509a38/ijms-21-09354-g001.jpg

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