E-MTAB-1643 - Transcription profiling by array of Doxorubicin (DOX)-resistant MCF7 breast cancer cells

Released on 1 June 2013, last updated on 3 June 2014
Homo sapiens
Samples (11)
Array (1)
Protocols (9)
Summary: Cancer imparts an increased risk for venous thromboembolism (VTE). Direct mechanisms linking VTE with malignancy remain unknown. Our characterization of Doxorubicin (DOX)-resistant MCF7 breast cancer cells revealed links with antithrombotic pathways, as an anticoagulant transcriptional profile was observed. Specifically, the intracellular anticoagulant Tissue Factor Pathway Inhibitor 1 (TFPI1) protein was elevated and functional in all resistant models tested; TFPI1 accumulation coincided with reduced thrombin. TFPI1 overexpression in unselected cells elevated pro-malignant gene markers and increased DOX resistance. Furthermore, TFPI1 and Breast Cancer Resistant Protein (BCRP) levels increased early and remained sustained during selection. Finally, consistent with antithrombin-mediated hypoxic metastasis, Hypoxia-Inducible Factor 1 alpha (HIF1alpha) was elevated in drug resistant and TFPI1 overexpressing cells. Thus, increased TFPI1 may create an intratumoral hypoxic environment, potentially leading to drug resistance. MCF7 cells were selected for DOX resistance by first treating the cells with 1 microM DOX for 48 hours. The cells were then exposed to 100 nM DOX for 2 weeks. After this period, the surviving cells were resistant to further DOX treatment.
Experiment types
transcription profiling by array, compound treatment design, dose response design
TFPI1 Mediates Resistance to Doxorubicin in Breast Cancer Cells by Inducing a Hypoxic-Like Response. Davies GF, Berg A, Postnikoff SD, Wilson HL, Arnason TG, Kusalik A, Harkness TA. PLoS One 9(1):e84611 (2014), Europe PMC 24489651
TFPI1 mediates resistance to doxorubicin in breast cancer cells by inducing a hypoxic-like response. Davies GF, Berg A, Postnikoff SD, Wilson HL, Arnason TG, Kusalik A, Harkness TA. :e84611 (2014), Europe PMC 24489651
Investigation descriptionE-MTAB-1643.idf.txt
Sample and data relationshipE-MTAB-1643.sdrf.txt
Raw data (1)E-MTAB-1643.raw.1.zip
Processed data (1)E-MTAB-1643.processed.1.zip
Array designA-MEXP-1173.adf.txt