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由Pten缺失或激活型Pik3ca突变驱动的乳腺肿瘤的共同特征和独特特征。

Common and distinct features of mammary tumors driven by Pten-deletion or activating Pik3ca mutation.

作者信息

Liu Jeff C, Wang Dong-Yu, Egan Sean E, Zacksenhaus Eldad

机构信息

Division of Advanced Diagnostics, Toronto General Research Institute - University Health Network, Toronto, Ontario, Canada.

Princess Margaret Cancer Center, Toronto, Ontario, Canada.

出版信息

Oncotarget. 2016 Feb 23;7(8):9060-8. doi: 10.18632/oncotarget.6985.

DOI:10.18632/oncotarget.6985
PMID:26814435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4891026/
Abstract

PTEN loss and PIK3CA activation both promote the accumulation of phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). While these proteins also have distinct biochemical functions, beyond the regulation of PIP3, little is known about the consequences of these differences in vivo. Here, we directly compared cancer signalling in mammary tumors from MMTV-Cre:Ptenf/f and MMTV-Cre:Pik3ca(LSL-H1047R) mice. Using unsupervised hierarchical clustering we found that whereas MMTV-Cre:Pik3ca(LSL-H1047R)-derived tumors fall into two separate groups, designated squamous-likeEx and class14(Ex), MMTV-Cre:Ptenf/f tumors cluster as one group together with PIK3CA(H1047R) class14(Ex), exhibiting a 'luminal' expression profile. Gene Set Enrichment Analysis (GSEA) of Pten(Δ)ˆ† and PIK3CA(H1047R) class14(Ex) tumors revealed very similar profiles of signalling pathways as well as some interesting differences. Analysis of 18 signalling signatures revealed that PI3K signalling is significantly induced whereas EGFR signalling is significantly reduced in Pten(∆) versus PIK3CA(H1047R) tumors. Thus, Pten(∆) and PIK3CA(H1047R) tumors exhibit discernable differences that may impact tumorigenesis and response to therapy.

摘要

PTEN缺失和PIK3CA激活均会促进磷脂酰肌醇(3,4,5)-三磷酸(PIP3)的积累。虽然这些蛋白也具有不同的生化功能，但除了对PIP3的调节外，对于这些差异在体内的后果知之甚少。在此，我们直接比较了MMTV-Cre:Ptenf/f和MMTV-Cre:Pik3ca(LSL-H1047R)小鼠乳腺肿瘤中的癌症信号传导。通过无监督层次聚类，我们发现，MMTV-Cre:Pik3ca(LSL-H1047R)衍生的肿瘤分为两个独立的组，分别命名为鳞状样Ex和class14(Ex)，而MMTV-Cre:Ptenf/f肿瘤与PIK3CA(H1047R) class14(Ex)聚为一组，表现出“管腔”表达谱。对Pten(Δ)和PIK3CA(H1047R) class14(Ex)肿瘤进行基因集富集分析(GSEA)，结果显示信号通路谱非常相似，但也存在一些有趣的差异。对18种信号特征的分析表明，与PIK3CA(H1047R)肿瘤相比，Pten(∆)肿瘤中PI3K信号显著诱导，而EGFR信号显著降低。因此Pten(∆)和PIK3CA(H1047R)肿瘤表现出明显差异，这可能会影响肿瘤发生和对治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/1652092321e1/oncotarget-07-9060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/e1b58546ab60/oncotarget-07-9060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/27dd45bea744/oncotarget-07-9060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/34b06004be9c/oncotarget-07-9060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/1652092321e1/oncotarget-07-9060-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/e1b58546ab60/oncotarget-07-9060-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/27dd45bea744/oncotarget-07-9060-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/34b06004be9c/oncotarget-07-9060-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/4891026/1652092321e1/oncotarget-07-9060-g004.jpg

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