Nuclear Her2 contributes to paclitaxel resistance in breast cancer cells
| Autor: | Xin-Jun Liang, Yaojun Feng, Ding-Feng Huang, Juan Xu, Xin-Hong Wu, Qu Zhang, Hong-Mei Zheng, Bo Luo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Paclitaxel Receptor ErbB-2 Survivin Apoptosis Breast Neoplasms Importin Karyopherins chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor Humans Pharmacology (medical) skin and connective tissue diseases neoplasms Cell Nucleus Pharmacology Chemistry Transfection Oncology Drug Resistance Neoplasm Cancer research Female Nuclear transport Nuclear localization sequence |
| Zdroj: | Anti-Cancer Drugs. |
| ISSN: | 0959-4973 |
| DOI: | 10.1097/cad.0000000000001048 |
| Popis: | Translocation of full-length Her2 receptor into nucleus was reported by some studies. Here, we tested whether nuclear Her2 contributes to paclitaxel resistance in Her2-overexpressing breast cancer cells. Breast cancer cell was transfected with plasmids containing cDNA of wild-type Her2 or mutant-type Her2 lacking the nuclear localization signal (NLS) sequence which is required for Her2 nuclear transport. Cell resistance to paclitaxel was analyzed. Paclitaxel-resistant breast cancer cell was also developed and nuclear Her2 expression was tested. Then, correlation between nuclear Her2 and resistance to paclitaxel were analyzed. Expression of importin β1 was decreased to downregulate nuclear Her2 level and cell resistance to paclitaxel was tested. We found that Her2 overexpression increases Her2 nuclear expression and cells resistance to paclitaxel in MCF-7 cells. In the paclitaxel resistant cell (SK-BR-3/R), nuclear Her2 expression is upregulated compared with parental SK-BR-3 cells. Increased expression of nuclear Her2 after short-time (48 h) treatment of paclitaxel was also observed in SK-BR-3 cells. Further downregulation of Her2 nuclear expression through blocking expression of importin β1 sensitizes the cells to paclitaxel. The analysis showed that the Her2 nuclear expression increases the survivin expression which leads to resistance to paclitaxel. Her2 nuclear expression decreases paclitaxel-induced apoptosis. However, co-immunoprecipitation was applied, and the physical interaction of nuclear Her2 and survivin was not detected. We show for the first time that nuclear Her2 contributes to paclitaxel resistance in breast cancer cells which suggests that nuclear Her2 as a potential target to sensitize breast cancers to paclitaxel treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|