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逆转录病毒感染通过扩增醛脱氢酶(ALDH1)阳性的干细胞样群体来增加MDA-MB-231乳腺癌细胞的致瘤潜能。

Retroviral-infection increases tumorigenic potential of MDA-MB-231 breast carcinoma cells by expanding an aldehyde dehydrogenase (ALDH1) positive stem-cell like population.

作者信息

Wegman-Points Lauren J, Teoh-Fitzgerald Melissa L T, Mao Gaowei, Zhu Yueming, Fath Melissa A, Spitz Douglas R, Domann Frederick E

机构信息

Department of Health and Human Physiology, University of Iowa, Iowa City, IA 52240, United States ; Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52240, United States.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States ; Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52240, United States.

出版信息

Redox Biol. 2014 Jun 24;2:847-54. doi: 10.1016/j.redox.2014.06.006. eCollection 2014.

Abstract

Retroviral transformation has been associated with pro-proliferative oncogenic signaling in human cells. The current study demonstrates that transduction of human breast carcinoma cells (MDA-MB231) with LXSN and QCXIP retroviral vectors causes significant increases in growth rate, clonogenic fraction, and aldehyde dehydrogenase-1 positive cells (ALDH1+), which is associated with increased steady-state levels of cancer stem cell populations. Furthermore, this retroviral-induced enhancement of cancer cell growth in vitro was also accompanied by a significant increase in xenograft tumor growth rate in vivo. The retroviral induced increases in cancer cell growth rate were partially inhibited by treatment with 100 U/ml polyethylene glycol-conjugated-(PEG)-superoxide dismutase and/or PEG-catalase. These results show that retroviral infection of MDA-MB231 human breast cancer cells is capable of enhancing cell proliferation and cancer stem cell populations as well as suggesting that modulation of reactive oxygen species-induced pro-survival signaling pathways may be involved in these effects.

摘要

逆转录病毒转化与人类细胞中的促增殖致癌信号传导有关。当前研究表明,用LXSN和QCXIP逆转录病毒载体转导人乳腺癌细胞(MDA-MB231)会导致生长速率、克隆形成率和醛脱氢酶-1阳性细胞(ALDH1+)显著增加,这与癌症干细胞群体的稳态水平升高有关。此外,这种逆转录病毒在体外诱导的癌细胞生长增强也伴随着体内异种移植肿瘤生长速率的显著增加。用100 U/ml聚乙二醇缀合的(PEG)超氧化物歧化酶和/或PEG过氧化氢酶处理可部分抑制逆转录病毒诱导的癌细胞生长速率增加。这些结果表明,MDA-MB231人乳腺癌细胞的逆转录病毒感染能够增强细胞增殖和癌症干细胞群体,同时表明活性氧诱导的促生存信号通路的调节可能参与了这些效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ab5/4085353/4fa94ed0a963/gr1.jpg

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