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Project description:Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.
2018-10-23 | GSE117495 | GEO
Project description:SMAD2 binding regions in breast cancer cell line and RNA-seq transcriptome analyses in T47D
| PRJNA482337 | ENA
Project description:SMAD2 binding regions in estrogen receptor-positive breast cancer cell line, T47D
| PRJNA482344 | ENA
Project description:Inhibitors for cyclin-dependent kinase (CDK) 4 and CDK6 have been established as effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although the CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we have focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor Palbociclib and Activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal-type breast cancer cell line T47D. Mechanistically, Palbociclib enhanced SMAD2 binding to the genome through inhibiting linker phosphorylation of the SMAD2 protein by CDK4/6. Comparison of the SMAD2 ChIP-seq data of T47D with those of a triple-negative breast cancer cell line Hs578T indicated that Palbociclib augments different SMAD2-mediated program defined based on types of cells, and enhances SMAD2 binding to the target regions on the genome without affecting its binding pattern. Collectively, the CDK4/6 inhibitor facilitates the cytostatic effects of Activin-SMAD2, while it also enhances its tumor promoting effects depending on types of breast cancer.
2018-10-23 | GSE117496 | GEO
Project description:SMAD2 binding regions in triple negative breast cancer cell line, Hs578T
| PRJNA482343 | ENA
Project description:Background: Breast cancer is the second leading cause of death in women. Alternative medicine with high efficacy is needed for breast cancer treatments, for example induction of apoptosis using natural products. It has been found that many natural apoptosis-inducing compounds are isolated from marine sponge. The objective of this study is to analyze the ability of extracts of the sponge Ancorina sp. to induce apoptosis on human breast cancer T47D cell line and find out its mechanism. Methods: T47D cells were treated with crude extracts of methanol, dichloromethane:methanol (1:1) and dichloromethane Ancorina sp. for 24 h, and doxorubicin was used as a positive control. Methods used for this study were MTT assay to examine cell viability and determine IC 50 of the three extracts, while the percentage of apoptosis and caspase-3 were investigated by flow cytometry. Results: IC 50 values of methanol, dichloromethane:methanol (1:1), and dichloromethane extract were 84.25, 121.45, and 99.85?g/mL respectively. The percentages of apoptotic cells after treatment with methanol, dichloromethane:methanol (1:1), and dichloromethane extracts were 88.68, 27.54 and 53.63% respectively, whereas the percentage of caspase-3 was 77.87, 12.66 and 12.97%, respectively. Conclusions: These results revealed that all extracts of Ancorina sp. have strong or moderate cytotoxicity and have the ability to induce apoptosis on T47D human breast cancer cell line. However, methanol crude extract has high efficacy to induce apoptosis through caspase-3 activation compared to the other extracts. Hence methanol extract warrants further investigation as a natural medicine for human breast cancer.
| S-EPMC6468741 | biostudies-literature
Project description:T47D and MCF7 are two human hormone-dependent breast cancer cell lines which are widely used as experimental models for in vitro and in vivo (tumor xenografts) breast cancer studies. Several proteins involved in cancer development were identified in these cell lines by proteomic analyses. Although these studies reported the proteomic profiles of each cell line, until now, their differential protein expression profiles have not been established. Here, we used two-dimensional gel and mass spectrometry analyses to compare the proteomic profiles of the two cell lines, T47D and MCF7. Our data revealed that more than 164 proteins are differentially expressed between them. According to their biological functions, the results showed that proteins involved in cell growth stimulation, anti-apoptosis mechanisms and cancerogenesis are more strongly expressed in T47D than in MCF7. These proteins include G1/S-specific cyclin-D3 and prohibitin. Proteins implicated in transcription repression and apoptosis regulation, including transcriptional repressor NF-X1, nitrilase homolog 2 and interleukin-10, are, on the contrary, more strongly expressed in MCF7 as compared to T47D. Five proteins that were previously described as breast cancer biomarkers, namely cathepsin D, cathepsin B, protein S100-A14, heat shock protein beta-1 (HSP27) and proliferating cell nuclear antigen (PCNA), are found to be differentially expressed in the two cell lines. A list of differentially expressed proteins between T47D and MCF7 was generated, providing useful information for further studies of breast cancer mechanisms with these cell lines as models.
| S-EPMC3286449 | biostudies-literature
Project description:Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.
| S-EPMC3713872 | biostudies-literature
Project description:An array CGH hybridization of breast cancer cell line T47D compared against a normal human female reference.
2010-06-25 | GSE22547 | GEO
Project description:We performed genome-wide PADI2 ChIP seq experiments in T47D cell lines and also RNP2 ChIP seq in T47D cells only expressing HA Tagged amanitin resistant wild type in comparison to R1810A mutant form of RNAP2.
2018-11-21 | GSE105793 | GEO