Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane-treated human breast epithelial cells reveals common expression profiles
| Autor: | Patrick G. Shaw, Akhilesh Pandey, Raghothama Chaerkady, Thomas W. Kensler, Nancy E. Davidson, Kala Visvanathan, Abena S. Agyeman |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Proteome Microarray Biology Article Cell Line Transcriptome chemistry.chemical_compound Isothiocyanates Stable isotope labeling by amino acids in cell culture NAD(P)H Dehydrogenase (Quinone) Anticarcinogenic Agents Humans Breast Oligonucleotide Array Sequence Analysis Gene knockdown Kelch-Like ECH-Associated Protein 1 Proteomic Profiling Gene Expression Profiling Intracellular Signaling Peptides and Proteins Epithelial Cells Aldehyde Dehydrogenase Molecular biology Up-Regulation Gene expression profiling Alcohol Oxidoreductases Oncology chemistry Gene Knockdown Techniques Sulfoxides Female RNA Interference Thiocyanates Drug metabolism Sulforaphane |
| Zdroj: | Breast Cancer Research and Treatment. 132:175-187 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-011-1536-9 |
| Popis: | Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a potent inhibitor of experimental mammary carcinogenesis and may be an effective, safe chemopreventive agent for use in humans. SFN acts in part on the Keap1/Nrf2 pathway to regulate a battery of cytoprotective genes. In this study, transcriptomic and proteomic changes in the estrogen receptor negative, non-tumorigenic human breast epithelial MCF10A cell line were analyzed following SFN treatment or KEAP1 knockdown with siRNA using microarray and stable isotopic labeling with amino acids in culture (SILAC), respectively. Changes in selected transcripts and proteins were confirmed by PCR and Western blot in MCF10A and MCF12A cells. There was strong correlation between the transcriptomic and proteomic responses in both the SFN treatment (R = 0.679, P < 0.05) and KEAP1 knockdown (R = 0.853, P < 0.05) experiments. Common pathways for SFN treatment and KEAP1 knockdown were xenobiotic metabolism and antioxidants, glutathione metabolism, carbohydrate metabolism, and NADH/NADPH regeneration. Moreover, these pathways were most prominent in both the transcriptomic and the proteomic analyses. The aldo–keto reductase family members, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, as well as NQO1 and ALDH3A1, were highly upregulated at both the transcriptomic and the proteomic levels. Collectively, these studies served to identify potential biomarkers that can be used in clinical trials to investigate the initial pharmacodynamic action of SFN in the breast. |
| Databáze: | OpenAIRE |
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