JunB can enhance the transcription of IL-8 in oral squamous cell carcinoma
| Autor: | Mai Fukasawa, Anna Nishihara, Masatake Asano, Mariko Tsunoda, Leo Takada |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Transcription Genetic Physiology JUNB Proto-Oncogene Proteins c-jun Clinical Biochemistry Cell macromolecular substances Transfection Small hairpin RNA 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Secretion RNA Messenger Promoter Regions Genetic Transcription factor Chemistry Activator (genetics) c-jun Interleukin-8 Cell Biology Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Carcinoma Squamous Cell Mouth Neoplasms Proto-Oncogene Proteins c-fos Transcription Factors |
| Zdroj: | Journal of cellular physiologyREFERENCES. 236(1) |
| ISSN: | 1097-4652 |
| Popis: | Proteasome inhibitor MG132 was shown to enhance the secretion of interleukin 8 (IL-8) by various cells. The enhancement is regulated by the transcription factor activator protein-1 (AP-1) at the transcriptional level. AP-1 is a dimer formed by AP-1 family proteins. The purpose of the present study was to explore the combinations of the AP-1 family proteins that contribute to MG132-driven IL-8 secretion. Oral squamous cell carcinoma-derived cell lines, Ca9-22 and HSC3, were used to demonstrate their response to MG132. IL-8 secretion was augmented by MG132 in both cell lines. c-Jun expression was detected in both the cell lines, whereas c-Fos expression was detected only in the HSC3. The influence of MG132 stimulation on c-Jun and c-Fos expression was further examined by western blot analysis. c-Jun expression was increased by MG132 stimulation, whereas c-Fos expression was not detected even after MG132 stimulation. As JunB is reported to inhibit the transcriptional activity of the AP-1 complex, we speculated that the c-Jun homodimer should contribute to IL-8 enhancement. Expression vectors encoding wild type and c-Jun mutants, M17 and M22-23, respectively, were constructed and transfected into the Ca9-22 cells. In contrast to our expectations, MG132-induced IL-8 secretion was significantly reduced in all the transfectants suggesting that other c-Jun members might form homodimers with c-Jun and contribute to IL-8 enhancement. Transfection of the cells with c-Jun or JunB small hairpin RNA (shRNA) reduced IL-8 secretion up to 50% and 65% of the control shRNA transfectant. Furthermore, cotransfection of both shRNA almost completely inhibited the IL-8 secretion. These results indicate that JunB not only inhibits but also enhances the transcription of c-Jun targets in combination with c-Jun. |
| Databáze: | OpenAIRE |
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