Somatic mutation and gain of copy number of PIK3CA in human breast cancer.
Somatic mutation and gain of copy number of PIK3CA in human breast cancer.
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DOI：
10.1186/bcr1262
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Sidransky D
中科院分区：
文献类型：
--
作者：
Wu G;Xing M;Mambo E;Huang X;Liu J;Guo Z;Chatterjee A;Goldenberg D;Gollin SM;Sukumar S;Trink B;Sidransky D
磷脂酰肌醇3-激酶（PI 3 Ks）是一组调节参与细胞增殖、粘附、存活和运动的信号传导途径的脂质激酶。尽管PIK 3CA扩增和体细胞突变先前已在各种人类癌症中报道，但人类乳腺癌中PIK 3CA的遗传变化尚未明确确定。使用15个乳腺癌细胞系和92个原发性乳腺肿瘤（33个具有匹配的正常组织）来检查PIK 3CA的体细胞突变和基因拷贝数。在体细胞突变研究中，我们特别检查了外显子1、9和20，据报道这些外显子是结肠癌的热点。对于基因拷贝数的分析，我们使用定量实时PCR和荧光原位杂交。我们还用PIK 3CA抑制剂LY 294002处理了几种乳腺癌细胞，并比较了有和没有PIK 3CA突变的细胞的凋亡状态。我们在原发性乳腺肿瘤和细胞系中分别确定了20.6%（19/92）和33.3%（5/15）的PIK 3CA体细胞突变频率。我们还发现，8.7%（8/92）的肿瘤携带PIK 3CA基因拷贝数增加。在这项研究中，只有四个病例同时包含基因拷贝数增加和体细胞突变。此外，PIK 3CA的突变与一些乳腺癌细胞中Akt磷酸化的状态以及PIK 3CA突变的乳腺癌细胞中PIK 3CA诱导的凋亡增加的抑制相关。PIK 3CA的体细胞突变而不是基因拷贝数的增加是导致人类乳腺癌进展的常见遗传改变。PIK 3CA内的频繁和聚集突变使其成为用于早期检测的有吸引力的分子标记物和乳腺癌中有希望的治疗靶点。
Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer.
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影响因子：
3.6
作者：
Bachman, KE;Argani, P;Park, BH
通讯作者：
Park, BH
影响因子：
4.8
作者：
Ayala-Torres, S;Chen, YM;Van Houten, B
通讯作者：
Van Houten, B
DOI：
10.1073/pnas.94.2.514
发表时间：
1997-01-21
影响因子：
11.1
作者：
Yakes, FM;VanHouten, B
通讯作者：
VanHouten, B
影响因子：
8.8
作者：
Rooney, PH;Murray, GI;Stevenson, DAJ;Haites, NE;Cassidy, J;McLeod, HL
通讯作者：
McLeod, HL
DOI：
10.1073/pnas.0408864102
发表时间：
2005-01-18
影响因子：
11.1
作者：
Kang, SY;Bader, AG;Vogt, PK
通讯作者：
Vogt, PK