CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer.
CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer.
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DOI：
10.1016/j.molonc.2008.09.004
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发表时间：
2008-12
影响因子：
6.6
通讯作者：
Pollack JR
中科院分区：
文献类型：
--
作者：
Bergamaschi A;Kim YH;Kwei KA;La Choi Y;Bocanegra M;Langerød A;Han W;Noh DY;Huntsman DG;Jeffrey SS;Børresen-Dale AL;Pollack JR
乳腺癌表现出临床和分子异质性，其中表达谱研究已经确定了五种主要的分子亚型。基底样亚型表达基底上皮标志物，且雌激素受体（ER）、孕激素受体（PR）和HER 2呈阴性，与较高的DNA拷贝数变异（CNA）总体水平、特异性CNA（如染色体上的增加）相关10 p）和预后不良。发现肿瘤亚型的分子遗传学基础可能为治疗提供新的机会。为了确定与基底细胞样肿瘤相关的10 p驱动癌基因，我们分析了172例乳腺癌的基因组图谱。最小的共享增益区域仅跨越10 p13处的7个基因，包括钙/钙调蛋白依赖性蛋白激酶ID（CAMK 1D），其在细胞内信号传导中起作用，但先前与癌症无关。通过微阵列，CAMK 1D扩增时过表达，并通过免疫组化显示，与原位癌相比，在浸润性癌中表达升高。CAMK 1D在非致瘤性乳腺上皮细胞中的工程化过表达导致细胞增殖增加，以及指示上皮-间充质转化（EMT）的分子和表型改变，包括细胞-细胞粘附的丧失和细胞迁移和侵袭增加。我们的研究结果将CAMK 1D确定为与乳腺癌EMT相关的新型扩增癌基因，并作为与临床上不利的基底样肿瘤特别相关的潜在治疗靶点。
Breast cancer exhibits clinical and molecular heterogeneity, where expression-profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new opportunities for therapy. To identify the driver oncogene on 10p associated with basal-like tumors, we analyzed genomic profiles of 172 breast carcinomas. The smallest shared region of gain spanned just seven genes at 10p13, including calcium/calmodulin-dependent protein kinase ID (CAMK1D), functioning in intracellular signaling but not previously linked to cancer. By microarray, CAMK1D was overexpressed when amplified, and by immunohistochemistry exhibited elevated expression in invasive carcinomas compared to carcinoma in situ. Engineered overexpression of CAMK1D in non-tumorigenic breast epithelial cells led to increased cell proliferation, and molecular and phenotypic alterations indicative of epithelial-mesenchymal transition (EMT), including loss of cell-cell adhesions and increased cell migration and invasion. Our findings identify CAMK1D as a novel amplified oncogene linked to EMT in breast cancer, and as a potential therapeutic target with particular relevance to clinically unfavorable basal-like tumors.
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斯坦福微阵列数据库：新分析工具的实现和软件的开源发布。
影响因子：
14.9
作者：
Demeter, Janos;Beauheim, Catherine;Gollub, Jeremy;Hernandez-Boussard, Tina;Jin, Heng;Maier, Donald;Matese, John C.;Nitzberg, Michael;Wymore, Farrell;Zachariah, Zachariah K.;Brown, Patrick O.;Sherlock, Gavin;Ball, Catherine A.
通讯作者：
Ball, Catherine A.
影响因子：
4.8
作者：
Kahl, CR;Means, AR
通讯作者：
Means, AR
影响因子：
4.4
作者：
Kapp, Amy V.;Jeffrey, Stefanie S.;Langerod, Anita;Borresen-Dale, Anne-Lise;Han, Wonshik;Noh, Dong-Young;Bukholm, Ida R. K.;Nicolau, Monica;Brown, Patrick O.;Tibshirani, Robert
通讯作者：
Tibshirani, Robert
DOI：
10.1186/bcr1675
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Langerød A;Zhao H;Borgan Ø;Nesland JM;Bukholm IR;Ikdahl T;Kåresen R;Børresen-Dale AL;Jeffrey SS
通讯作者：
Jeffrey SS
影响因子：
3
作者：
Lai C;Horlings HM;van de Vijver MJ;van Beers EH;Nederlof PM;Wessels LF;Reinders MJ
通讯作者：
Reinders MJ