Project description:This SuperSeries is composed of the following subset Series: GSE18952: Effects of IGF 1 on primary breast fibroblasts (normal and carcinoma associated) GSE18953: Effects of IGF 1 on MCF-7 breast cancer cells GSE18954: Effects of IGF 1 on CCL-171 fibroblasts Refer to individual Series
Project description:Although estrogen receptor (ER) and insulin-like growth factor (IGF) signaling are important for normal mammary development and breast cancer, cross-talk between these pathways, particularly at the level of gene transcription, remains poorly understood. We performed microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr. IGF-I regulated mRNA of 5-10-fold more genes than estradiol, and many genes were co-regulated by both ligands. Importantly, expression of these co-regulated genes correlated with poor prognosis of human breast cancer. Closer examination revealed enrichment of repressed transcripts. Interestingly, a number of potential tumor suppressors were down-regulated by IGF-I and estradiol. In fact, BLNK, one of the top repressed genes, is a potential growth suppressor in breast cancer cells. Analysis of three down-regulated genes showed that E2-mediated repression occurred independently of IGF-IR, and IGF-I-mediated repression occurred independently of ER. However, repression by IGF-I or estradiol required common downstream kinases. In conclusion, E2 and IGF-I co-regulate a set of genes that affect breast cancer outcome. There is enrichment of repressed transcripts, and the down-regulation is independent at the receptor level. This may be important clinically, as tumors with active ER and IGF-IR signaling may require co-targeting of both pathways. KEYWORDS: multiple group comparison Microarray analysis on MCF-7 breast cancer cells treated with estradiol (E2) or IGF-I for 3hr or 24hr.
Project description:To characterize the effects of IGF 1 on MCF 7 breast cancer cells, we cultured pre-starved MCF 7 cells with or without 50ng/ml IGF 1 for 24 h. We then profiled gene expression changes using Human Exonic Evidence Based Oligonucleotide (HEEBO) microarrays. After stimulation, total RNA was extracted and amplified using a modified Eberwine procedure. The amplified RNA was labeled with the fluorescent dye Cy5 and pooled with Cy3 labeled reference RNA, and then the pooled RNA was hybridized onto HEEBO microarrays. After hybridization and washing, arrays were scanned on a fluorescent microscope scanner.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:To characterize the effects of IGF 1 on MCF 7 breast cancer cells, we cultured pre-starved MCF 7 cells with or without 50ng/ml IGF 1 for 24 h. We then profiled gene expression changes using Human Exonic Evidence Based Oligonucleotide (HEEBO) microarrays. After stimulation, total RNA was extracted and amplified using a modified Eberwine procedure. The amplified RNA was labeled with the fluorescent dye Cy5 and pooled with Cy3 labeled reference RNA, and then the pooled RNA was hybridized onto HEEBO microarrays. After hybridization and washing, arrays were scanned on a fluorescent microscope scanner. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract.
Project description:breast cancer. Combined IGF and estrogen-targeted therapy may improve the benefit of hormonal therapy alone. We employed a postmenopausal model of estrogen-dependent breast cancer in vitro and in vivo using the aromatase-expressing MCF-7/AC-1cells. Using this model, we investigated the anti-tumor effects of the dual IGF-1R/InsR tyrosine kinase inhibitor, BMS-754807 alone and in combination with letrozole or tamoxifen in vivo. We used microarrays to compare gene expression changes of MCF7 breast xenograft treated with either BMS754807, or Tamoxifen or Letrozole alone; or Tamoxifen or Letrozole in combination with BMS754807 for 28 days