2021 Fiscal Year Research-status Report
Modulation of circadian clock and its therapeutic implications in invasive breast carcinoma
| Project/Area Number |
20K17585
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | breast carcinoma / metastasis / circadian clock |
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| Outline of Annual Research Achievements |
Based on our previous data, we made efforts to analyze the correlation of glut1 with those genes belong to the gene ontology of circadian rhythm in human invasive breast carcinoma TCGA database. Remarkably we found that the top five negatively correlated genes with glut1 (SLC2A1) were Cry2, RORC, Sirt1, OGT and Per2, where as top five positively correlated genes were HDAC2, HDAC1, PPP1CB, LGR4 and NAMPT. These findings suggest us, alteration in glucose uptake could be associated with the modulation of circadian clock genes in association with the modification in the histone acetylation. Therefore, we would like to check the alteration of genes/protein associated with histone acetylation during the modulation of circadian clock in mouse and human breast carcinoma.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We are conducting experiment step by step. After getting the in vitro data regarding the histone acetylation we will conduct animal experiment.
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| Strategy for Future Research Activity |
1. Following modulation of circadin clock genes either by D-allose or sodium butyrate in mouse and human breast cacinoma cells, we will check the staus of clock genes as well as genes associated with histone acetylation to observe the epigeneitc changes.
2. Clock genes-modulated breast cancer cells (1x106) will be injected in the mammary fat pad of 6-weeks-old female immunodeficient nude (MDAMB-
231) and/or Balb/C mice (4T1 cell line). Metastatic potential (migrated cells foci) of clock genes-manipulated breast cancer cells will be
analyzed in the lungs of xenograft mice following fixation in Bouin’s solution in accordance with our standardized protocol.
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