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MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response.

MEN1 缺乏导致肺癌的神经内分泌分化并破坏DNA损伤反应。

  • 影响因子:0
  • DOI:10.1038/s41467-020-14614-4
  • 作者列表:"Qiu H","Jin BM","Wang ZF","Xu B","Zheng QF","Zhang L","Zhu LY","Shi S","Yuan JB","Lin X","Gao SB","Jin GH
  • 发表时间:2020-02-21
Abstract

:The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1-/- driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.

摘要

: MEN1 基因,一种编码menin蛋白的肿瘤抑制基因,在神经内分泌 (NE) 肿瘤中发生高频率突变; 然而,该基因在体内NE型肺癌中的生物学重要性仍不清楚。在这里,我们建立了ATII特异性KrasG12D/+/Men1-/驱动的基因工程小鼠模型,表明menin的缺乏导致DNA损伤的积累,并拮抗致癌Kras诱导的衰老和肺肿瘤发生过程中的上皮-间质转化。在某些人原发性肺癌中menin表达的丧失与升高的NE谱和降低的总生存期相关。

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METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

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影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
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肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

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