Project description:In this research, we use DNA microarray analysis to clarify the gene expression responses in Jurkat cells after Tamoxifen treatment. Jurkat cells are a dexamethasone-resistant cell line derived from a T-cell Acute Lymphoblastic Leukaemia sample in relapse
Project description:Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with ER-positive breast cancer. However, there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner. In this study we assessed gene expression changes at multiple time points (days 1, 2, 4, 7, 14) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis, proliferation and angiogenesis within 2 days of therapy. Hierarchical clustering identified six time-related gene expression patterns, which separated into three groups: two with early/transient responses, two with continuous/late responses and two with variable response patterns. The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation (e.g. BUB1B, CCNA2, CDKN3, MKI67, UBE2C), whereas the continuous/late changed genes represented the more classical estrogen response genes (e.g.TFF1, TFF3, IGFBP5). Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer. The profiles of genes that were most differentially expressed on days 2, 4 and 7 following treatment were able to predict prognosis, whereas those most changed on days 1 and 14 were not, in four tamoxifen treated datasets representing a total of 404 patients. Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner. Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies. Tamoxifen treated ZR-75 xenograft samples compared to a pooled control. 5 timepoints, replicates and dye swaps, giving a total of 32 arrays
Project description:Tamoxifen is the most widely prescribed anti-estrogen treatment for patients with ER-positive breast cancer. However, there is still a need for biomarkers that reliably predict endocrine sensitivity in breast cancers and these may well be expressed in a dynamic manner. In this study we assessed gene expression changes at multiple time points (days 1, 2, 4, 7, 14) after tamoxifen treatment in the ER-positive ZR-75-1 xenograft model that displays significant changes in apoptosis, proliferation and angiogenesis within 2 days of therapy. Hierarchical clustering identified six time-related gene expression patterns, which separated into three groups: two with early/transient responses, two with continuous/late responses and two with variable response patterns. The early/transient response represented reductions in many genes that are involved in cell cycle and proliferation (e.g. BUB1B, CCNA2, CDKN3, MKI67, UBE2C), whereas the continuous/late changed genes represented the more classical estrogen response genes (e.g.TFF1, TFF3, IGFBP5). Genes and the proteins they encode were confirmed to have similar temporal patterns of expression in vitro and in vivo and correlated with reduction in tumour volume in primary breast cancer. The profiles of genes that were most differentially expressed on days 2, 4 and 7 following treatment were able to predict prognosis, whereas those most changed on days 1 and 14 were not, in four tamoxifen treated datasets representing a total of 404 patients. Both early/transient/proliferation response genes and continuous/late/estrogen-response genes are able to predict prognosis of primary breast tumours in a dynamic manner. Temporal expression of therapy-response genes is clearly an important factor in characterising the response to endocrine therapy in breast tumours which has significant implications for the timing of biopsies in neoadjuvant biomarker studies.
Project description:The cultured cell line Jurkat is frequently employed in studies of T cell function. Here we identified the microRNAs expressed in Jurkat cells in the presence and absence of CD3/CD28mAb treatment.
Project description:The cultured cell line Jurkat is frequently employed in studies of T cell function. Here we identified the microRNAs expressed in Jurkat cells in the presence and absence of CD3/CD28mAb treatment. Analyzed the expression of microRNAs extracted from untreated Jurkat cells as a control and Jurkat cells treated with CD3/CD28mAb.
Project description:In order to increase the spectral library to study the ocurrence of distinct peptide fragmetation patterns, we analyzed the whole cell proteome of Jurkat cells.
Project description:Tamoxifen enhances romidepsin-induced senescence in pancreatic cancer cells. We compared gene-expression profile among untreated control, romidepsin-treated, tamoxifen-treated, and romidepsin plus tamoxifen-treated Panc1 cells.
Project description:K562 cells, a myeloid leukemia cells line, were engineered to express a tamoxifen inducible dominant negative Myb (MERT). K562-MERT cells were cultured for 3 days in the absence and presence of 1 uM tamoxifen. The RNA was then extracted from the untreated and tamoxifen treated K562-MERT cells and submitted to Incyte Genomics for poly(A) RNA selection, probe preparation, hybridization of the labeled cDNA to the micorarray chip (Incyte Genomics) and data analysis.
Project description:The primary objective is, first, the comparison of tamoxifen and anastrozole and, second, the comparison of zoledronate added to standard adjuvant therapy with controls according to disease-free survival (DFS) in premenopausal patients with non-metastatic breast cancer treated with tamoxifen or anastrozole. To assess whether zoledronate added to standard adjuvant therapy can decrease or even prevent bone loss in patients treated with hormonal blockade combined with an antiestrogen or aromatase inhibitor.