Molecular mechanisms of PI3K isoform dependence in embryonic growth.

IF 1.2 Q3 OBSTETRICS & GYNECOLOGY
Sena Atıcı, Onur Çizmecioğlu
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引用次数: 0

Abstract

Objective: The phosphoinositide 3-kinase (PI3K) pathway is an important signaling mechanism for cell proliferation and metabolism. Mutations that activate PIK3CA may make cells p110α dependent, but when phosphatase tensin homolog (PTEN) is lost, the p110β isoform of PI3Ks becomes more important. However, the exact mechanism underlying the prevalence of p110s remains unclear. In this study, our aim was to elucidate the processes behind PI3K isoform dependency in a cellular model of embryonic development.

Material and methods: In order to understand PI3K isoform prevalence, mouse embryonic fibroblasts (MEFs) were used and p110β, PTEN and Rac1 activity was modulated using retroviral plasmids. Expression levels and cellular growth were assessed by performing immunoblots and crystal violet assays.

Results: The levels of PTEN had only a partial effect on the prevalence of PI3K isoforms in MEFs. The dependency on p110α diminished when PTEN was depleted. Of note, when PTEN expression was repressed, there was no full transition in dependency from one PI3K isoform to the other. Interestingly, the viability of PTEN-depleted MEFs became less dependent on p110α and more dependent on p110β when p110β was overexpressed. Nevertheless, the overexpression of p110β in conjunction with PTEN knock-downs did not result in a complete shift of isoforms in PI3Ks. Finally, we investigated Rac1 activation with a mutant allele and determined a more potent increase in p110β prominence in MEFs.

Conclusion: These findings suggest that multiple cellular parameters, including PTEN status, PI3K isoform levels, and Rac1 activity, combine to influence PI3K isoform prevalence, rather than a single determinant.

胚胎生长过程中 PI3K 同工酶依赖性的分子机制
目的:磷酸肌酸 3-激酶(PI3K)通路是细胞增殖和新陈代谢的重要信号机制。激活 PIK3CA 的突变可能使细胞依赖 p110α,但当磷酸酶天丝同源物(PTEN)丢失时,PI3Ks 的 p110β 异构体变得更加重要。然而,p110s普遍存在的确切机制仍不清楚。在本研究中,我们的目的是在胚胎发育的细胞模型中阐明 PI3K 同工酶依赖性背后的过程:为了了解 PI3K 同工酶的流行情况,我们使用了小鼠胚胎成纤维细胞(MEFs),并使用逆转录病毒质粒调节 p110β、PTEN 和 Rac1 的活性。通过免疫印迹和水晶紫检测评估了表达水平和细胞生长情况:结果:PTEN的水平只对MEFs中PI3K同工酶的流行率产生部分影响。当PTEN被耗尽时,对p110α的依赖性减弱。值得注意的是,当 PTEN 的表达受到抑制时,对一种 PI3K 同工酶的依赖并没有完全转变为对另一种 PI3K 同工酶的依赖。有趣的是,当过量表达 p110β 时,PTEN 缺失的 MEFs 对 p110α 的依赖性降低,而对 p110β 的依赖性增加。然而,过表达 p110β 和敲除 PTEN 并没有导致 PI3Ks 同工酶的完全转变。最后,我们用一个突变等位基因研究了 Rac1 的活化情况,并确定 p110β 在 MEFs 中的显著性有了更强的提高:这些发现表明,多种细胞参数(包括 PTEN 状态、PI3K 同工酶水平和 Rac1 活性)共同影响 PI3K 同工酶的流行,而不是单一的决定因素。
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来源期刊
CiteScore
2.40
自引率
7.10%
发文量
56
期刊介绍: Journal of the Turkish-German Gynecological Association is the official, open access publication of the Turkish-German Gynecological Education and Research Foundation and Turkish-German Gynecological Association and is published quarterly on March, June, September and December. It is an independent peer-reviewed international journal printed in English language. Manuscripts are reviewed in accordance with “double-blind peer review” process for both reviewers and authors. The target audience of Journal of the Turkish-German Gynecological Association includes gynecologists and primary care physicians interested in gynecology practice. It publishes original works on all aspects of obstertrics and gynecology. The aim of Journal of the Turkish-German Gynecological Association is to publish high quality original research articles. In addition to research articles, reviews, editorials, letters to the editor, diagnostic puzzle are also published. Suggestions for new books are also welcomed. Journal of the Turkish-German Gynecological Association does not charge any fee for article submission or processing.
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