Modulation of circadian clock and its therapeutic implications in invasive breast carcinoma
| Project/Area Number |
20K17585
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
|---|
| Research Institution | Kagawa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | breast carcinoma / metastasis / circadian clock |
|---|
| Outline of Research at the Start |
The outline of research is as follows:
FY 2020: a) Overexpression of PER1 and PER2. c) Cell proliferation (WST-1) and cytotoxicity (LDH) assay. d) Protease activity and adhesion assays; cell aggregation, migration and invasion assays. e) Gene analysis of adhesome and degradome.
FY 2021: In vivo studies with clock genes-manipulated breast cancer cells.
FY 2022: a) Virtual screening to recognize the ligands against the identified targets. b) Therapeutic effectiveness of the identified ligands in vitro. c) therapeutic efficacy of the identified ligands in xenograft mouse model.
|
| Outline of Final Research Achievements |
Our data indicated that Per1 and Per2 mRNA expression decreased in breast carcinoma cells compared to normal mammary tissue in mice. Since glucose metabolism has a significant impact on clock genes, we conducted pharmacological studies with rare sugar, D-allose. Cell proliferation was reduced after treatment with D-allose in mouse and human breast carcinoma cells. The gene expression data revealed that Per1, Per2 and Cry2 expression were increased after treatment with D-allose compared to the vehicle or D-glucose treatment. Based on our previous data, we analyzed the correlation of glut1 with those genes belong to the gene ontology of circadian rhythm. Interestingly, our data indicated that treatment with D-allose reduced the HDAC1 and HDAC2 gene expression compared to the control or equimolar D-glucose. Therefore, these data are in line with our hypothesis that modulation of circadian clock might be a potential therapeutic approach for invasive breast carcinoma.
|
| Academic Significance and Societal Importance of the Research Achievements |
Alteration of clock genes is highly associated with cancer cell proliferation and metastasis. Therefore, our findings indicated that modulating the circadian clock could be a remedial approach for attenuating metastasis as well as improved outcomes in patients with invasive breast carcinoma.
|
Report
(4 results)
Research Products
(2 results)
