Sequestosome 1 (p62) accumulation in breast cancer cells suppresses progesterone receptor expression via argonaute 2
| Autor: | Naoharu Takano, Masaya Miyazaki, Ayuka Yokota, Mayumi Tokuhisa, Hirotsugu Hino, Keisuke Miyazawa, Masaki Hiramoto, Hiromi Kazama |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Biophysics Breast Neoplasms Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Sequestosome 1 Breast cancer Cell Line Tumor Sequestosome-1 Protein Gene expression Progesterone receptor medicine Humans education Molecular Biology Cell Nucleus education.field_of_study Gene knockdown Cancer Signal transducing adaptor protein Cell Biology Argonaute medicine.disease Gene Expression Regulation Neoplastic Protein Transport 030104 developmental biology 030220 oncology & carcinogenesis Argonaute Proteins Cancer research Female Receptors Progesterone |
| Zdroj: | Biochemical and Biophysical Research Communications. 531:256-263 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.07.058 |
| Popis: | Sequestosome 1 (p62) is a multifunctional adapter protein involved in various physiological functions, such as selective autophagy and oxidative stress response. Hence, aberrant expression and defective regulation of p62 are thought to lead to the onset of various diseases, including cancer. The expression of p62 has been shown to be increased in breast cancer tissues, and is correlated with a poor prognosis. However, the role of p62 in the breast cancer pathophysiology is still unclear. Here, we aimed to analyze the effect of changes in p62 expression on breast cancer cell lines. DNA microarray analysis revealed that the expression of progesterone receptor (PR), which is one of the indices for the classification of breast cancer subtypes, was markedly suppressed by forced expression of p62. The protein expression of PR was also decreased by forced expression of p62, but increased by knockdown of p62. Moreover, we found that p62 knockdown induced the protein expression of argonaute 2 (AGO2). Luciferase reporter assay results showed that the gene expression of PR was promoted by AGO2. Furthermore, results revealed that overexpression of AGO2 partially rescued the decrease in PR expression induced by forced expression of p62. Collectively, our findings indicated that p62 accumulation suppressed the expression of AGO2, which in turn decreased the expression of PR, suggesting that p62 may serve as a marker of aggressive breast cancer and poor prognosis. Moreover, the p62-AGO2-PR axis was identified as a crucial signaling cascade in breast cancer progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect