人們知道限制飲食對嚙齒類動物有抗癌效果已有幾十年了，但令人吃驚的是,，我們對決定某種腫瘤是否會對節(jié)食措施產(chǎn)生反應(yīng)的分子機制卻知之甚少,。
Nada Kalaany 和David Sabatini報告，某些人類癌細(xì)胞系,，當(dāng)在小鼠體內(nèi)作為腫瘤異體移植物生長時,，對于飲食限制的抗生長效應(yīng)非常敏感，而人類的其他癌細(xì)胞系則對此有抵抗力?，F(xiàn)在，造成腫瘤不同敏感度的原因,，已被發(fā)現(xiàn)是“phosphatidylinositol-3-kinase (PI3K)/Akt”信號通道的活化狀態(tài),。因此，這一通道的狀態(tài)可能是指示哪些腫瘤會對模仿飲食限制的治療方法產(chǎn)生反應(yīng)的一個指示器,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 458, 725-731 (9 April 2009) | doi:10.1038/nature07782
Tumours with PI3K activation are resistant to dietary restriction
Nada Y. Kalaany1,2,3 & David M. Sabatini1,2,3,4
1 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
2 Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3 Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
4 Broad Institute, Seven Cambridge Center, Cambridge, Massachusetts 02142, USA
AbstractDietary restriction delays the incidence and decreases the growth of various types of tumours, but the mechanisms underlying the sensitivity of tumours to food restriction remain unknown. Here we show that certain human cancer cell lines, when grown as tumour xenografts in mice, are highly sensitive to the anti-growth effects of dietary restriction, whereas others are resistant. Cancer cells that form dietary-restriction-resistant tumours carry mutations that cause constitutive activation of the phosphatidylinositol-3-kinase (PI3K) pathway and in culture proliferate in the absence of insulin or insulin-like growth factor 1. Substitution of an activated mutant allele of PI3K with wild-type PI3K in otherwise isogenic cancer cells, or the restoration of PTEN expression in a PTEN-null cancer cell line, is sufficient to convert a dietary-restriction-resistant tumour into one that is dietary-restriction-sensitive. Dietary restriction does not affect a PTEN-null mouse model of prostate cancer, but it significantly decreases tumour burden in a mouse model of lung cancer lacking constitutive PI3K signalling. Thus, the PI3K pathway is an important determinant of the sensitivity of tumours to dietary restriction, and activating mutations in the pathway may influence the response of cancers to dietary restriction-mimetic therapies.
