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非人灵长类动物胃癌发生过程中SRC家族酪氨酸激酶的失调

Deregulation of the SRC Family Tyrosine Kinases in Gastric Carcinogenesis in Non-human Primates.

作者信息

DE Fátima Ferreira Borges DA Costa Joana, DE Castro Sant' Anna Carla, Muniz José Augusto Pereira Carneiro, DA Rocha Carlos Alberto Machado, Lamarão Letícia Martins, DE Fátima Aquino Moreira Nunes Caroline, DE Assumpção Paulo Pimentel, Burbano Rommel Rodriguez

机构信息

Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.

Laboratory of Molecular Biology, Ophir Loyola Hospital, Belém, Brazil

出版信息

Anticancer Res. 2018 Nov;38(11):6317-6320. doi: 10.21873/anticanres.12988.

Abstract

BACKGROUND/AIM: The evolution of gastric carcinogenesis remains largely unknown, as the regulatory mechanisms involved in the aggressiveness of gastric cancer are still poorly understood. Kinases are downstream modulators and effectors of various cell signaling cascades and play key roles in the development of neoplastic diseases. The objective of this study was to evaluate the expression of genes and proteins of the SRC family, including FYN, YES, BLK, FGR, LYN and SRC, in a model of intestinal gastric carcinogenesis generated by treating Cebus apella, a New World non-human primate, with N-methyl nitrosourea (MNU).

MATERIALS AND METHODS

mRNA expression of genes was measured by real-time reverse transcription quantitative PCR (RT-qPCR) and protein expression was measured by western blotting in six Cebus apella treated with N-methyl-nitrosourea (MNU) for about 2.5 years.

RESULTS

Elevated mRNA and protein expression mainly of the SRC and LYN kinases was observed. Their expression was gradually increasing as non-atrophic gastritis was evolving to gastric cancer.

CONCLUSION

SRC family kinases play a key role in tumor progression and metastasis and may be a promising target for the treatment of gastric cancer.

摘要

背景/目的:胃癌发生的演变在很大程度上仍不清楚,因为参与胃癌侵袭性的调控机制仍知之甚少。激酶是各种细胞信号级联反应的下游调节剂和效应器,在肿瘤性疾病的发展中起关键作用。本研究的目的是评估SRC家族基因和蛋白的表达,包括FYN、YES、BLK、FGR、LYN和SRC,该评估是在通过用N-甲基亚硝基脲(MNU)处理新世界非人灵长类动物僧帽猴所产生的肠型胃癌发生模型中进行的。

材料与方法

通过实时逆转录定量PCR(RT-qPCR)测量基因的mRNA表达,并通过蛋白质印迹法测量在用N-甲基亚硝基脲(MNU)处理约2.5年的六只僧帽猴中的蛋白质表达。

结果

观察到主要是SRC和LYN激酶的mRNA和蛋白质表达升高。随着非萎缩性胃炎演变为胃癌,它们的表达逐渐增加。

结论

SRC家族激酶在肿瘤进展和转移中起关键作用,可能是治疗胃癌的一个有前景的靶点。

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