有哪些信誉好的足球投注网站an integrated bioinformatics approach identifies elevated cyclin e2 expression and e2f activity as distinct features of tamoxifen resistant breast tumors综合生物信息学方法识别细胞周期蛋白升高e2表达和e2f耐他莫昔芬乳腺癌肿瘤的活动不同的特征.pdfVIP
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an integrated bioinformatics approach identifies elevated cyclin e2 expression and e2f activity as distinct features of tamoxifen resistant breast tumors综合生物信息学方法识别细胞周期蛋白升高e2表达和e2f耐他莫昔芬乳腺癌肿瘤的活动不同的特征
An Integrated Bioinformatics Approach Identifies
Elevated Cyclin E2 Expression and E2F Activity as Distinct
Features of Tamoxifen Resistant Breast Tumors
1 2 2 1
Lei Huang , Shuangping Zhao , Jonna M. Frasor *, Yang Dai *
1 Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States of America, 2 Department of Physiology and Biophysics, University of
Illinois at Chicago, Chicago, Illinois, United States of America
Abstract
Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endocrine therapy. Here we used
an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an
attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic
strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast
tumors were identified from three different publically available microarray datasets. These differentially expressed (DE)
genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors.
The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules
and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially
expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three
datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as
elevated activity of E2F transcription factors, and were highly correlated with a Luminal i
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