Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast.
Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast.
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DOI：
10.1038/onc.2009.463
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发表时间：
2010-03-25
期刊：
影响因子：
8
通讯作者：
Friedl, A.
中科院分区：
文献类型：
--
作者：
Bauer, M.;Su, G.;Casper, C.;He, R.;Rehrauer, W.;Friedl, A.
乳腺癌侵袭与间质成纤维细胞的显着变化相关。癌相关成纤维细胞（CAF）支持并促进肿瘤发生，而正常乳腺成纤维细胞（NF）被认为抑制肿瘤进展。关于CAF和NF之间的基因表达差异或基因表达的患者间变异性知之甚少。配对CAF和NF分离自六个原发性人乳腺癌标本。从CAF和NF的低传代培养物中提取RNA，并使用Affytechnic Human Genome U133 Plus 2.0阵列进行分析。用经验贝叶斯模型检查阵列数据，并根据等效表达的后验概率和表达的倍数差异进行过滤。与NF相比，21个基因（27个探针组）在CAF中上调。这些基因的已知功能涉及旁分泌或细胞内信号传导、转录调节、细胞外基质和细胞粘附/迁移。10个基因（14个探针组）在CAF中下调，包括多能性转录因子KLF 4。10个基因的定量RT-PCR分析验证了阵列结果。三种基因产物的免疫组织化学染色证实了基质表达的位置和相对数量。令人惊讶的是，NF中基因表达的变异性略高于CAF，表明正常间质的个体间异质性。
Breast carcinoma invasion is associated with prominent alterations in stromal fibroblasts. Carcinoma-associated fibroblasts (CAF) support and promote tumorigenesis, whereas normal mammary fibroblasts (NF) are thought to suppress tumor progression. Little is known about the difference in gene expression between CAF and NF or the patient-to-patient variability in gene expression. Paired CAF and NF were isolated from six primary human breast carcinoma specimens. RNA was extracted from low-passage cultures of CAF and NF and analyzed with Affymetrix Human Genome U133 Plus 2.0 arrays. The array data were examined with an empirical Bayes model and filtered according to the posterior probability of equivalent expression and fold difference in expression. Twenty-one genes (27 probe sets) were up-regulated in CAF, as compared to NF. Known functions of these genes relate to paracrine or intracellular signaling, transcriptional regulation, extracellular matrix and cell adhesion/migration. Ten genes (14 probe sets) were down-regulated in CAF, including the pluripotency transcription factor KLF4. Quantitative RT-PCR analysis of 10 genes validated the array results. Immunohistochemical staining for three gene products confirmed stromal expression in terms of location and relative quantity. Surprisingly, the variability of gene expression was slightly higher in NF than in CAF, suggesting inter-individual heterogeneity of normal stroma.
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影响因子：
3.6
作者：
Mercier I;Casimiro MC;Wang C;Rosenberg AL;Quong J;Minkeu A;Allen KG;Danilo C;Sotgia F;Bonuccelli G;Jasmin JF;Xu H;Bosco E;Aronow B;Witkiewicz A;Pestell RG;Knudsen ES;Lisanti MP
通讯作者：
Lisanti MP
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
2
作者：
Kendziorski, CM;Newton, MA;Gould, MN
通讯作者：
Gould, MN
影响因子：
50.3
作者：
Allinen, M;Beroukhim, R;Polyak, K
通讯作者：
Polyak, K
影响因子：
30.8
作者：
Hu, M;Yao, J;Polyak, K
通讯作者：
Polyak, K