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| Status |
Public on Jun 09, 2017 |
| Title |
Development of chemically modified peptide targeting BIG3-PHB2 interaction on estrogen-dependent breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Our previous studies demonstrated that specific inhibition of the BIG3-PHB2 complex, which is indispensable for estrogen (E2)-signaling activation, using ERAP, a dominant-negative peptide inhibitor, leads to the suppression of E2-dependent breast cancer cell growth in vitro and in vivo. However, duration of its effect is very short for clinical use. Here, we developed the chemically modified ERAP using stapling methods (stERAP; stapled ERAP) to improve duration of their antitumor effects. Tumor bearing mice treated with every 4 and 7 days with stERAP (1 mg/kg body weight) treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERalpha. This event led to the complete suppression of the E2-signalling pathways and ERalpha-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that the chemically modified stERAP may be a promising anti-tumor drug to suppress the growth of luminal-type breast cancer in clinical use.
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| Overall design |
Up- and down-regulated genes by treatment of stapled-peptide or unspecific stapled-peptide at 24 and 48 hours was measured.
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| Contributor(s) |
Yoshimaru T, Katagiri T, Matsushita Y |
| Citation(s) |
28500289 |
| Submission date |
Sep 27, 2016 |
| Last update date |
Jan 09, 2018 |
| Contact name |
Tetsuro Yoshimaru |
| E-mail(s) |
tmaru@genome.tokushima-u.ac.jp
|
| Phone |
+81-88-633-9476
|
| Organization name |
Tokushima University
|
| Department |
Institute for Genome Research
|
| Lab |
Division of Genome Medicine
|
| Street address |
3-18-15 Kuramoto-cho
|
| City |
Tokushima |
| ZIP/Postal code |
770-8503 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA344561 |
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